272 results on '"Chou ST"'
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2. Epidemiological investigation of a case of nosocomial Legionnaires' disease in Taiwan: implications for routine environmental surveillance
- Author
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Chou St, Lin Hh, Chien St, Ben Rj, Cher-Min Fong, Lee Tm, Chiang Cs, Yusen E. Lin, Shih Hy, Hsueh Jc, and Tseng Lr
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Genotype ,Legionella ,Taiwan ,routine environmental cultures ,Legionella pneumophila ,Epidemiological investigation hospital water supply ,Epidemiology ,Pulsed-field gel electrophoresis ,Environmental Microbiology ,Medicine ,Humans ,Intensive care medicine ,Cross Infection ,Molecular Epidemiology ,Molecular epidemiology ,biology ,business.industry ,Sputum ,General Medicine ,PFGE ,nosocomial legionellosis ,biology.organism_classification ,medicine.disease ,bacterial infections and mycoses ,DNA Fingerprinting ,Subtyping ,Hospitals ,respiratory tract diseases ,Bacterial Typing Techniques ,Infectious Diseases ,Emergency medicine ,bacteria ,Legionnaires' disease ,medicine.symptom ,Legionnaires' Disease ,business ,Pneumonia (non-human) - Abstract
An epidemiological investigation with Legionella and molecular subtyping was conducted to determine the source of a case of nosocomial Legionnaires' disease (LD) who was hospitalized in three hospitals within a month. Legionella pneumophila serogroup 3, an uncommon serogroup for infection, was isolated from the patient's sputum. Environmental surveillance revealed Legionella colonization in all three hospitals; the patient isolate matched the isolate from the first hospital by molecular typing. Culturing the hospital water supply for Legionella is a pro-active strategy for detection of nosocomial LD even in hospitals experiencing no previous cases.
- Published
- 2009
3. A putative role for bile duct epithelial cells in chronic duck hepatitis B (DHBV) infection
- Author
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Nicoll, AJ, primary, Locarnini, SA, additional, Luscombe, CA, additional, Doultree, JC, additional, Marshall, JA, additional, Chou, ST, additional, Angus, PW, additional, and Smallwood, RA, additional
- Published
- 1995
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4. Isolation of substances with antiproliferative and apoptosis-inducing activities against leukemia cells from the leaves of Zanthoxylum ailanthoides Sieb. & Zucc.
- Author
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Chou ST, Chan HH, Peng HY, Liou MJ, Wu TS, Chou, Su-Tze, Chan, Hsiu-Hui, Peng, Hsin-Yi, Liou, Meei-Jen, and Wu, Tian-Shung
- Abstract
Extraction of the leaves of Zanthoxylum ailanthoides Sieb. & Zucc. affords extracts and four isolated compounds which exhibit activities against leukemia cells. The chloroform-soluble fraction (ZAC) of the crude extract of this plant showed cytotoxic activity against human promyelocytic leukemia (HL-60) and myelomonocytic leukemia (WEHI-3) cells with IC(50) values of 73.06 and 42.22 μg/mL, respectively. The active ZAC was further separated to yield pheophorbide-a methyl ester (1), pheophorbide-b methyl ester (2), 13(2)-hydroxyl (13(2)-S) pheophorbide-a methyl ester (3) and 13(2)-hydroxyl (13(2)-R) pheophorbide-b methyl ester (4) whose structures were confirmed by spectroscopic methods. Compounds 2-4 showed cytotoxic activities against both leukemia cells with IC(50) value in the range of 46.76-79.43 nM, whereas compound 1 exhibited only weak cytotoxic activity. The extracts and compounds 1-4 also induced apoptosis and DNA damage in leukemia cells after treatment. The results suggested that the Z. ailanthoides is biologically active against leukemia cells. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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5. In vitro Antioxidant and Antiproliferative Activity of the Stem Extracts from Graptopetalum paraguayense.
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Chen SJ, Chung JG, Chung YC, and Chou ST
- Abstract
This study was aimed to evaluate the antioxidant abilities of water (SGWE), 50% ethanolic (SGE50) and 95% ethanolic (SGE95) extracts from the stem of Graptopetalum paraguayense, and the extract with the highest antioxidant activity was assayed for its inhibitory effect on proliferation of human hepatoma (Hep G2) cell line. Antioxidant abilities of extracts were assessed their radical-scavenging abilities and effects on Fe/ascorbate-induced lipid peroxidation in a liposome model system. The results of this study showed that antioxidant activities were increased with the increase of the extracts concentrations, and the activities correlated with both the total phenol and anthocyanin contents. A comparison of the 50% inhibition concentration (IC(50)) values of different antioxidant reactions revealed that SGWE was the more effective at scavenging superoxide anion radical and preventing lipid peroxidation than SGE50 and SGE95 (p < 0.05). The flow cytometry results indicated that SGWE lowered cell viability, and induced G1 phase arrest and apoptosis in Hep G2 cells. These results demonstrated the antioxidatant and anti-hepatoma potential of stem of Graptopetalum paraguayense. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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6. Positive heterophile antibody test and massive splenomegaly in an adolescent with previously unsuspected Gaucher disease.
- Author
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Chou ST, Shah SS, Hodinka RL, Cohen AR, Chou, Stella T, Shah, Samir S, Hodinka, Richard L, and Cohen, Alan R
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- 2004
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7. Effect of Riboflavin Deficiency on the Metabolism of Oxypurines in Chicks
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Chou St
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Male ,Xanthine Oxidase ,medicine.medical_specialty ,animal structures ,Physiology ,Riboflavin ,Growth ,Biology ,Kidney ,chemistry.chemical_compound ,Riboflavin Deficiency ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Paralysis ,Hypoxanthine ,Pharmacology ,Body Weight ,Broiler ,food and beverages ,Organ Size ,General Medicine ,Metabolism ,Xanthine ,Diet ,Uric Acid ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,Xanthine dehydrogenase ,Purines ,Hypoxanthines ,Uric acid ,Female ,Chickens - Abstract
Day-old broiler chicks of both sexes were used in three experiments to determine the effect of riboflavin deficiency on oxypurine metabolism catalyzed by xanthine dehydrogenase, a riboflavin-containing enzyme. Chicks fed a riboflavin-deficient diet (1.38 mg/kg) for 3 weeks exhibited depressed growth and a high incidence of curled-toe paralysis (higher than 80%) as compared to control chicks (15.1 mg riboflavin per kilogram diet; no incidence of curled-toe paralysis). In addition, the precursors of uric acid, hypoxanthine and/or xanthine, accumulated in the liver and kidney of deficient chicks showing curled-toe paralysis. These observations show that dietary riboflavin being incorporated into xanthine dehydrogenase is essential for oxypurine metabolism. Moreover in the chick, the liver and the kidney may be important sites of uric acid synthesis. The low uric acid concentration in the plasma of the deficient chicks appeared to be indicative of a disturbance in uric acid synthesis in the liver and kidney.
- Published
- 1971
8. Relative importance of liver and kidney in synthesis of uric acid in chickens
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Chou St
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Urinary system ,Biology ,Kidney ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Inosine Nucleotides ,Hypoxanthine ,Pharmacology ,chemistry.chemical_classification ,Broiler ,Age Factors ,General Medicine ,Organ Size ,Xanthine ,Uric Acid ,Inosinic acid ,Enzyme ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Liver ,Hypoxanthines ,Xanthines ,Uric acid ,Chickens - Abstract
Broiler chickens of 1, 2, and 7 months of age were used for enzymatic spectrophotometric determination of uric acid and its precursors, xanthine, hypoxanthine, and inosinic acid, in the liver and kidney in an attempt to show the relative importance of the two organs in the synthesis of uric acid, the major nitrogenous compound excreted by birds.Uric acid concentration of the kidney was two to three times as high as the liver, probably attributable in part to preformed uric acid trapped in the urinary passages in the kidney. Significantly higher concentrations of xanthine, hypoxanthine, and inosinic acid were found in the kidney than in the liver. The calculations based on organ weight and the concentrations of uric acid precursors suggest that the kidney synthesizes 96, 60, and 73% as much uric acid as does the liver for the 1-, 2-, and 7-month-old chickens, respectively.
- Published
- 1972
9. Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis.
- Author
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Wilken MB, Fonar G, Qiu R, Bennett L, Tober J, Nations C, Pavani G, Tsao V, Garifallou J, Petit C, Maguire JA, Gagne A, Okoli N, Gadue P, Chou ST, French DL, Speck NA, and Thom CS
- Abstract
Tropomyosins coat actin filaments to impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. TPM1 has been shown to regulate blood cell formation in vitro, but it remains unclear how or when TPM1 affects hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, we found that TPM1 knockout augmented developmental cell state transitions and key signaling pathways, including tumor necrosis factor alpha (TNF-α) signaling, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses revealed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced HE formation during embryogenesis, without increasing the number of hematopoietic stem cells. These findings illuminate novel effects of TPM1 on developmental hematopoiesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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10. Genotyped RHD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D.
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Chou ST, Mewha J, Friedman DF, Lazariu V, Makrm S, Ochoa G, Vege S, and Westhoff CM
- Abstract
Anti-D can occur in D-positive patients who inherit RHD genetic variants encoding partial D antigen expression, but unexpected anti-D is also found in the plasma of patients with sickle cell disease who have conventional RHD gene(s) and are transfused with units from Black donors. These anti-D are likely stimulated by variant Rh expressed on donor cells, however patients with anti-D, regardless of cause, are transfused for a lifetime with D-negative (Rh-negative) blood. This results in significant increased use of Rh-negative units, especially for those requiring chronic transfusion, which can strain Rh-negative blood inventories. We tested whether D-positive patients who made anti-D and had conventional RhD by RHD genotyping could safely be returned to D-positive transfusions without anti-D reappearance or compromised RBC survival using RHD genotype-matched units from Black donors. Five patients receiving chronic red cell exchange received an increasing number of D-positive units per procedure with a total of 72 D-positive RHD genotyped units transfused, with no anti-D restimulation. Unexpected anti-C and anti-E were identified during the study associated with donors with variant RHCE alleles. RH genotyping of D-positive units for transfusion may improve use and allocation of valuable Black donor units and reduce demand for Rh-negative blood., (Copyright © 2024 American Society of Hematology.)
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- 2024
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11. Current advances in 2024: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee.
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Poston JN, Andrews J, Arya S, Chou ST, Cohn C, Covington M, Crowe EP, Goel R, Gupta GK, Haspel RL, Hess A, Ipe TS, Jacobson J, Khan J, Murphy M, O'Brien K, Pagano MB, Panigrahi AK, Salazar E, Saifee NH, Stolla M, Zantek ND, Ziman A, and Metcalf RA
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- 2024
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12. Consensus transfusion guidelines for a large neonatal intensive care network.
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Gilmore LE, Chou ST, Ghavam S, and Thom CS
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- Humans, Infant, Newborn, Practice Guidelines as Topic, Intensive Care Units, Neonatal standards, Intensive Care, Neonatal standards, Intensive Care, Neonatal methods, Blood Transfusion standards, Blood Transfusion methods, Consensus
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- 2024
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13. MEG3-Mediated Oral Squamous-Cell-Carcinoma-Derived Exosomal miR-421 Activates Angiogenesis by Targeting HS2ST1 in Vascular Endothelial Cells.
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Huang CY, Chou ST, Hsu YM, Chao WJ, Wu GH, Hsiao JR, Wang HD, and Shiah SG
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- Humans, Cell Line, Tumor, Vascular Endothelial Growth Factor Receptor-2 metabolism, Vascular Endothelial Growth Factor Receptor-2 genetics, Angiogenesis, MicroRNAs genetics, MicroRNAs metabolism, Exosomes metabolism, Exosomes genetics, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Mouth Neoplasms metabolism, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Human Umbilical Vein Endothelial Cells metabolism, Cell Movement genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Gene Expression Regulation, Neoplastic
- Abstract
Exosomal microRNAs (miRNAs) from cancer cells play a key role in mediating the oral squamous cell carcinoma (OSCC) microenvironment. The objective of this study was to investigate how the long non-coding RNA (lncRNA) MEG3 affects OSCC angiogenesis through exosomal miR-421. Global miRNA microarray analysis and quantitative real-time PCR (qRT-PCR) were performed to determine the level of miRNAs in OSCC cell-derived exosomes. Cell migration, invasion, tube formation, immunohistochemistry, and hemoglobin concentrations were used to study the effects of exosomal miR-421 in angiogenesis. Western blotting was used to determine the expression level of HS2ST1 and VEGFR2-related downstream proteins. MiRNA array and qRT-PCR identified the upregulation of miR-421 in OSCC cell-derived exosomes. Furthermore, exosomal miR-421 can be taken up by human umbilical vein endothelial cells (HUVECs) and then target HS2ST1 through VEGF-mediated ERK and AKT phosphorylation, thereby promoting HUVEC migration, invasion, and tube formation. Additionally, forced expression of the lncRNA MEG3 in OSCC cells reduced exosomal miR-421 levels and then increased HS2ST1 expression, thereby reducing the VEGF/VEGFR2 pathway in HUVECs. Our results demonstrate a novel mechanism by which lncRNA MEG3 can act as a tumor suppressor and regulate endothelial angiogenesis through the exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.
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- 2024
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14. Investigating the postoperative soft tissue changes in different vertical facial divergent patients with mandibular prognathism.
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Tseng YC, Wu TY, Lu CY, Chou ST, Lin SH, and Chen CM
- Abstract
Background/purpose: The extent of three-dimensional soft tissue changes in patients with varied facial skeletal patterns following mandibular setback surgery remains unclear. In this study, we aimed to investigate the postoperative changes in soft tissue chin thickness among mandibular prognathism patients, focusing on those presenting different divergence patterns, such as hyperdivergent and normodivergent patients., Materials and Methods: Cone-beam computed tomography images were obtained from 56 skeletal Class III patients who underwent only mandibular setback. Based on vertical craniofacial skeletal relationship, patients were divided into normodivergent group (27°
37°) group. The three-dimensional displacements of Infradentale (Id), B point (B), and Pogonion (Pog), the soft tissue thickness of Id-Li (Labrale inferius), B-B' (soft tissue B point), and Pog-Pog' (soft tissue Pog point) were measured. Factors influencing the change in soft tissue thickness were investigated., Results: Preoperative B-B' and Pog-Pog' thickness were significantly thinner in the hyperdivergent group than normodivergent group. Postoperative changes in B-B' and Pog-Pog' thickness were significantly larger in the hyperdivergent group than normodivergent group. A significant correlation was found between soft tissue thickness change (B-B' and Pog-Pog') and the preoperative soft tissue thickness and superior movement (B and Pog)., Conclusion: Hyperdivergent patients with skeletal class III have thinner preoperative soft tissue thickness (B-B' and Pog-Pog') than normodivergent patients in the preoperation. Postoperative changes in B-B' and Pog-Pog' thickness were significantly larger in the hyperdivergent group than normodivergent group. Postoperative superior movement of B and Pog correlated with postoperative change of soft tissue thickness., Competing Interests: None., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.) - Published
- 2024
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15. Human erythroid progenitors express antigen presentation machinery.
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Clements RL, Kennedy EA, Song D, Campbell A, An HH, Amses KR, Miller-Ensminger T, Addison MM, Eisenlohr LC, Chou ST, and Jurado KA
- Abstract
Early-life immune exposures can profoundly impact lifelong health. However, functional mechanisms underlying fetal immune development remain incomplete. Erythrocytes are not typically considered active immune mediators, primarily because erythroid precursors discard their organelles as they mature, thus losing the ability to alter gene expression in response to stimuli. Erythroid progenitors and precursors circulate in human fetuses and neonates. Although there is limited evidence that erythroid precursors are immunomodulatory, our understanding of the underlying mechanisms remains inadequate. To define the immunobiological role of fetal and perinatal erythroid progenitors and precursors, we analyzed single cell RNA-sequencing data and found that transcriptomics support erythroid progenitors as putative immune mediators. Unexpectedly, we discovered that human erythroid progenitors constitutively express Major Histocompatibility Complex (MHC) class II antigen processing and presentation machinery, which are hallmarks of specialized antigen presenting immune cells. Furthermore, we demonstrate that erythroid progenitors internalize and cleave foreign proteins into peptide antigens. Unlike conventional antigen presenting cells, erythroid progenitors express atypical costimulatory molecules and immunoregulatory cytokines that direct the development of regulatory T cells, which are critical for establishing maternal-fetal tolerance. Expression of MHC II in definitive erythroid progenitors begins during the second trimester, coinciding with the appearance of mature T cells in the fetus, and is absent in primitive progenitors. Lastly, we demonstrate physical and molecular interaction potential of erythroid progenitors and T cells in the fetal liver. Our findings shed light on a unique orchestrator of fetal immunity and provide insight into the mechanisms by which erythroid cells contribute to host defense.
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- 2024
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16. Machine learning to optimize automated RH genotyping using whole-exome sequencing data.
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Chang TC, Yu J, Wang Z, Hankins JS, Weiss MJ, Wu G, Westhoff CM, Chou ST, and Zheng Y
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- Humans, Anemia, Sickle Cell genetics, Anemia, Sickle Cell therapy, Genotyping Techniques methods, Alleles, Rh-Hr Blood-Group System genetics, Machine Learning, Exome Sequencing, Genotype
- Abstract
Abstract: Rh phenotype matching reduces but does not eliminate alloimmunization in patients with sickle cell disease (SCD) due to RH genetic diversity that is not distinguishable by serological typing. RH genotype matching can potentially mitigate Rh alloimmunization but comprehensive and accessible genotyping methods are needed. We developed RHtyper as an automated algorithm to predict RH genotypes using whole-genome sequencing (WGS) data with high accuracy. Here, we adapted RHtyper for whole-exome sequencing (WES) data, which are more affordable but challenged by uneven sequencing coverage and exacerbated sequencing read misalignment, resulting in uncertain predictions for (1) RHD zygosity and hybrid alleles, (2) RHCE∗C vs. RHCE∗c alleles, (3) RHD c.1136C>T zygosity, and (4) RHCE c.48G>C zygosity. We optimized RHtyper to accurately predict RHD and RHCE genotypes using WES data by leveraging machine learning models and improved the concordance of WES with WGS predictions from 90.8% to 97.2% for RHD and 96.3% to 98.2% for RHCE among 396 patients in the Sickle Cell Clinical Research and Intervention Program. In a second validation cohort of 3030 cancer survivors (15.2% Black or African Americans) from the St. Jude Lifetime Cohort Study, the optimized RHtyper reached concordance rates between WES and WGS predications to 96.3% for RHD and 94.6% for RHCE. Machine learning improved the accuracy of RH predication using WES data. RHtyper has the potential, once implemented, to provide a precision medicine-based approach to facilitate RH genotype-matched transfusion and improve transfusion safety for patients with SCD. This study used data from clinical trials registered at ClinicalTrials.gov as #NCT02098863 and NCT00760656., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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17. Single-cell transcriptomics reveal synergistic and antagonistic effects of T21 and GATA1s on hematopoiesis.
- Author
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Takasaki K, Wafula EK, Kumar SS, Smith D, Gagne AL, French DL, Thom CS, and Chou ST
- Abstract
Trisomy 21 (T21), or Down syndrome (DS), is associated with baseline macrocytic erythrocytosis, thrombocytopenia, and neutrophilia, and transient abnormal myelopoiesis (TAM) and myeloid leukemia of DS (ML-DS). TAM and ML-DS blasts both arise from an aberrant megakaryocyte-erythroid progenitor and exclusively express GATA1s, the truncated isoform of GATA1 , while germline GATA1s mutations in a non-T21 context lead to congenital cytopenias without a leukemic predisposition. This suggests that T21 and GATA1s perturb hematopoiesis independently and synergistically, but this interaction has been challenging to study in part due to limited human cell and murine models. To dissect the developmental impacts of GATA1s on hematopoiesis in euploid and T21 cells, we performed a single-cell RNA-sequencing timecourse on hematopoietic progenitors (HPCs) derived from isogenic human induced pluripotent stem cells differing only by chromosome 21 and/or GATA1 status. These HPCs were surprisingly heterogeneous and displayed spontaneous lineage skew apparently dictated by T21 and/or GATA1s. In euploid cells, GATA1s nearly eliminated erythropoiesis, impaired MK maturation, and promoted an immature myelopoiesis, while in T21 cells, GATA1s appeared to compete with the enhanced erythropoiesis and suppressed megakaryopoiesis driven by T21 to give rise to immature erythrocytes, MKs, and myeloid cells. T21 and GATA1s both disrupted temporal regulation of lineage-specific transcriptional programs and specifically perturbed cell cycle genes. These findings in an isogenic system can thus be attributed specifically to T21 and GATA1s and suggest that these genetic changes together enhance HPC proliferation at the expense of maturation, consistent with a pro-leukemic phenotype.
- Published
- 2024
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18. Meeting the transfusion needs of a patient with anti-En a requires an international effort.
- Author
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Chou ST, Nance ST, Mansfield P, Friedman DF, and Keller MA
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- Humans, Blood Transfusion, Blood Grouping and Crossmatching methods, Qatar, Male, Female, Blood Group Incompatibility immunology, Blood Group Antigens immunology, Blood Donors
- Abstract
This extraordinary case showcases the identification of a rare anti-En
a specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between the hospital blood bank in the United States, the home blood center in Qatar, the blood center Immunohematology Reference Laboratory, as well as the American Rare Donor Program (ARDP) and the International Society for Blood Transfusion (ISBT) International Rare Donor Panel. Ena is a high-prevalence antigen, and blood samples from over 200 individuals of the extended family in Qatar were crossmatched against the patient's plasma with one compatible En(a-) individual identified. The ISBT International Rare Donor Panel identified an additional donor in Canada, resulting in a total of two En(a-) individuals available to donate blood for the patient., (© 2024 Stella T. Chou et al., published by Sciendo.)- Published
- 2024
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19. How I Treat Challenging Transfusion Cases in Sickle Cell Disease.
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Chou ST and Hendrickson JE
- Abstract
Transfusion of red blood cells (RBCs) can be lifesaving for individuals living with sickle cell disease (SCD). However, alloimmunization following transfusion is more common with SCD than other patient populations, resulting in morbidity and mortality. Management of complications related to RBC alloantibodies, including delayed hemolytic transfusion reactions (DHTRs) and identifying compatible RBCs for future transfusions, remains a challenge for hematologists and transfusion medicine providers. Although transfusion guidelines from organizations including the American Society for Hematology provide general recommendations, individual cases remain challenging. Antibody evanescence and the lack of widespread RBC alloantibody data sharing across hospitals pose unique challenges, as do RH variants in both transfusion recipients and blood donors. Further, as potentially curative therapies require RBC transfusions to lower the hemoglobin S prior to cellular therapy collections and infusions, highly alloimmunized patients may be deemed ineligible. The cases described are representative of clinical dilemmas the authors have encountered and the approaches are as evidence-based as the literature and the authors' experiences allow. A future desired state is one in which RBC alloantibody data are efficiently shared across institutions, Rh alloimmunization can be mitigated, better treatments exist for DHTRs, and a label of "difficult to transfuse" does not prevent desired therapies., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
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20. Generation of red blood cells from induced pluripotent stem cells.
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Gunawardena N and Chou ST
- Subjects
- Humans, Cell Differentiation, Erythrocytes, Erythropoiesis, Blood Transfusion methods, Induced Pluripotent Stem Cells
- Abstract
Purpose of Review: Human induced pluripotent stem cells (iPSCs) are an attractive source to generate in-vitro-derived blood for use as transfusable and reagent red cells. We review recent advancements in the field and the remaining limitations for clinical use., Recent Findings: For iPSC-derived red blood cell (RBC) generation, recent work has optimized culture conditions to omit feeder cells, enhance red cell maturation, and produce cells that mimic fetal or adult-type RBCs. Genome editing provides novel strategies to improve cell yield and create designer RBCs with customized antigen phenotypes., Summary: Current protocols support red cell production that mimics embryonic and fetal hematopoiesis and cell yield sufficient for diagnostic RBC reagents. Ongoing challenges to generate RBCs for transfusion include recapitulating definitive erythropoiesis to produce functional adult-type cells, increasing scalability of culture conditions, and optimizing high-density manufacturing capacity., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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21. Application of artificial intelligence in lateral cephalometric analysis.
- Author
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Lee HT, Chiu PY, Yen CW, Chou ST, and Tseng YC
- Abstract
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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22. Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells.
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Pavani G, Klein JG, Nations CC, Sussman JH, Tan K, An HH, Abdulmalik O, Thom CS, Gearhart PA, Willett CM, Maguire JA, Chou ST, French DL, and Gadue P
- Subjects
- Humans, Erythropoiesis genetics, Erythrocytes, Cell Differentiation genetics, Erythroblasts metabolism, Induced Pluripotent Stem Cells
- Abstract
Abstract: During development, erythroid cells are produced through at least 2 distinct hematopoietic waves (primitive and definitive), generating erythroblasts with different functional characteristics. Human induced pluripotent stem cells (iPSCs) can be used as a model platform to study the development of red blood cells (RBCs) with many of the differentiation protocols after the primitive wave of hematopoiesis. Recent advances have established that definitive hematopoietic progenitors can be generated from iPSCs, creating a unique situation for comparing primitive and definitive erythrocytes derived from cell sources of identical genetic background. We generated iPSCs from healthy fetal liver (FL) cells and produced isogenic primitive or definitive RBCs which were compared directly to the FL-derived RBCs. Functional assays confirmed differences between the 2 programs, with primitive RBCs showing a reduced proliferation potential, larger cell size, lack of Duffy RBC antigen expression, and higher expression of embryonic globins. Transcriptome profiling by scRNA-seq demonstrated high similarity between FL- and iPSC-derived definitive RBCs along with very different gene expression and regulatory network patterns for primitive RBCs. In addition, iPSC lines harboring a known pathogenic mutation in the erythroid master regulator KLF1 demonstrated phenotypic changes specific to definitive RBCs. Our studies provide new insights into differences between primitive and definitive erythropoiesis and highlight the importance of ontology when using iPSCs to model genetic hematologic diseases. Beyond disease modeling, the similarity between FL- and iPSC-derived definitive RBCs expands potential applications of definitive RBCs for diagnostic and transfusion products., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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23. RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.
- Author
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Israelyan N, Vege S, Friedman DF, Zhang Z, Uter S, Fasano RM, Yee M, Piccone C, Kelly S, Hankins JS, Zheng Y, Westhoff CM, and Chou ST
- Subjects
- Young Adult, Humans, Child, Erythrocyte Transfusion adverse effects, Erythrocytes, Genotype, Isoantibodies, Rh-Hr Blood-Group System, Anemia, Sickle Cell genetics, Anemia, Sickle Cell therapy, Blood Group Antigens, Anemia, Hemolytic, Autoimmune etiology
- Abstract
Background: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors., Study Design and Methods: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays., Results: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens., Discussion: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors., (© 2024 AABB.)
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- 2024
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24. NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer.
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Taylor BC, Sun X, Gonzalez-Ericsson PI, Sanchez V, Sanders ME, Wescott EC, Opalenik SR, Hanna A, Chou ST, Van Kaer L, Gomez H, Isaacs C, Ballinger TJ, Santa-Maria CA, Shah PD, Dees EC, Lehmann BD, Abramson VG, Pietenpol JA, and Balko JM
- Subjects
- Humans, Animals, Mice, Immunotherapy methods, Killer Cells, Natural, CD8-Positive T-Lymphocytes, B7-H1 Antigen metabolism, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms genetics
- Abstract
Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell-directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates antitumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of natural killer (NK) cells in an IFNγ-dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-programmed death (PD) L1 therapy and increased NK:T-cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK-cell function. Combining anti-NKG2A and anti-PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tumor-infiltrating NK and CD8+ T cells. These results suggest that similar strategies may enhance patient benefit in clinical trials., Significance: Clinical resistance to immunotherapy is common in breast cancer, and many patients will likely require combination therapy to maximize immunotherapeutic benefit. This study demonstrates that heterogeneous MHC-I expression drives resistance to anti-PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance. This article is featured in Selected Articles from This Issue, p. 201., (©2023 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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25. BMI1 regulates human erythroid self-renewal through both gene repression and gene activation.
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McGrath KE, Koniski AD, Murphy K, Getman M, An HH, Schulz VP, Kim AR, Zhang B, Schofield TL, Papoin J, Blanc L, Kingsley PD, Westhoff CM, Gallagher PG, Chou ST, Steiner LA, and Palis J
- Abstract
The limited proliferative capacity of erythroid precursors is a major obstacle to generate sufficient numbers of in vitro-derived red blood cells (RBC) for clinical purposes. We and others have determined that BMI1, a member of the polycomb repressive complex 1 (PRC1), is both necessary and sufficient to drive extensive proliferation of self-renewing erythroblasts (SREs). However, the mechanisms of BMI1 action remain poorly understood. BMI1 overexpression led to 10 billion-fold increase BMI1-induced (i)SRE self-renewal. Despite prolonged culture and BMI1 overexpression, human iSREs can terminally mature and agglutinate with typing reagent monoclonal antibodies against conventional RBC antigens. BMI1 and RING1B occupancy, along with repressive histone marks, were identified at known BMI1 target genes, including the INK-ARF locus, consistent with an altered cell cycle following BMI1 inhibition. We also identified upregulated BMI1 target genes with low repressive histone modifications, including key regulator of cholesterol homeostasis. Functional studies suggest that both cholesterol import and synthesis are essential for BMI1-associated self-renewal. These findings support the hypothesis that BMI1 regulates erythroid self-renewal not only through gene repression but also through gene activation and offer a strategy to expand the pool of immature erythroid precursors for eventual clinical uses., Competing Interests: Competing interests The authors declare no competing interests.
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- 2024
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26. GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.
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Takasaki K and Chou ST
- Subjects
- Humans, Animals, Mutation, Thrombocytopenia genetics, Thrombocytopenia pathology, Thrombocytopenia metabolism, Cell Differentiation genetics, Mice, GATA1 Transcription Factor genetics, GATA1 Transcription Factor metabolism, Blood Platelets metabolism, Thrombopoiesis genetics, Megakaryocytes metabolism, Megakaryocytes cytology
- Abstract
GATA1 is a highly conserved hematopoietic transcription factor (TF), essential for normal erythropoiesis and megakaryopoiesis, that encodes a full-length, predominant isoform and an amino (N) terminus-truncated isoform GATA1s. It is consistently expressed throughout megakaryocyte development and interacts with its target genes either independently or in association with binding partners such as FOG1 (friend of GATA1). While the N-terminus and zinc finger have classically been demonstrated to be necessary for the normal regulation of platelet-specific genes, murine models, cell-line studies, and human case reports indicate that the carboxy-terminal activation domain and zinc finger also play key roles in precisely controlling megakaryocyte growth, proliferation, and maturation. Murine models have shown that disruptions to GATA1 increase the proliferation of immature megakaryocytes with abnormal architecture and impaired terminal differentiation into platelets. In humans, germline GATA1 mutations result in variable cytopenias, including macrothrombocytopenia with abnormal platelet aggregation and excessive bleeding tendencies, while acquired GATA1s mutations in individuals with trisomy 21 (T21) result in transient abnormal myelopoiesis (TAM) and myeloid leukemia of Down syndrome (ML-DS) arising from a megakaryocyte-erythroid progenitor (MEP). Taken together, GATA1 plays a key role in regulating megakaryocyte differentiation, maturation, and proliferative capacity. As sequencing and proteomic technologies expand, additional GATA1 mutations and regulatory mechanisms contributing to human diseases of megakaryocytes and platelets are likely to be revealed., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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27. Comparison of the transverse cranial base dimension in different craniofacial skeletal relationships: A cone-beam computed tomography study.
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Chou ST, Lin SH, Chen SC, Chen CM, and Tseng YC
- Abstract
Background/purpose: In comparing the cranial base's size, most cephalometric studies focused on the length and angle in the anteroposterior direction. However, investigating the anterior, middle, and posterior cranial base's transverse dimensions is challenging. This study aimed to investigate the transverse dimensions of the cranial base in different craniofacial skeletal patterns and sexes using cone-beam computed tomography (CBCT)., Materials and Methods: A total of 210 adults (105 males and 105 females), including three different skeletal relationships, were included in the study. The cranial base dimensions were measured on a three-dimensional image structure rendered by CBCT. Statistical methods included the Kappa statistic for analysis of consistency and reproducibility and the independent t -test for differences in cranial base dimensions between sexes. A general linear model (GLM) was used to compare the transverse size of the cranial base among skeletal Class I, II, and III groups. The Pearson correlation coefficient explored the correlation among the cranial base dimensions., Results: The cranial base dimensions did not differ significantly between skeletal Class I, II, and III. The more prominent cranial base size was found in males than females, except for the crista galli length (CGL) and cribriform ethmoid plate width (CEPW). The cranial base dimensions did not differ significantly between different skeletal relationships. Most dimensions have significant correlations in the middle and the posterior cranial base., Conclusion: The cranial base's transverse dimensions in Taiwanese adults show no significant differences between craniofacial skeletal relationships. In the middle and posterior cranial base, transverse measurements reveal significant sexual dimorphism., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)
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- 2024
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28. Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.
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Sit YT, Takasaki K, An HH, Xiao Y, Hurtz C, Gearhart PA, Zhang Z, Gadue P, French DL, and Chou ST
- Subjects
- Humans, GATA1 Transcription Factor genetics, Thrombopoiesis genetics, Down Syndrome genetics, Down Syndrome complications, Leukemia, Megakaryoblastic, Acute complications, Leukemia, Megakaryoblastic, Acute genetics
- Abstract
Patients with Down syndrome (DS), or trisomy 21 (T21), are at increased risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (ML-DS). Both TAM and ML-DS require prenatal somatic mutations in GATA1, resulting in the truncated isoform GATA1s. The mechanism by which individual chromosome 21 (HSA21) genes synergize with GATA1s for leukemic transformation is challenging to study, in part due to limited human cell models with wild-type GATA1 (wtGATA1) or GATA1s. HSA21-encoded DYRK1A is overexpressed in ML-DS and may be a therapeutic target. To determine how DYRK1A influences hematopoiesis in concert with GATA1s, we used gene editing to disrupt all 3 alleles of DYRK1A in isogenic T21 induced pluripotent stem cells (iPSCs) with and without the GATA1s mutation. Unexpectedly, hematopoietic differentiation revealed that DYRK1A loss combined with GATA1s leads to increased megakaryocyte proliferation and decreased maturation. This proliferative phenotype was associated with upregulation of D-type cyclins and hyperphosphorylation of Rb to allow E2F release and derepression of its downstream targets. Notably, DYRK1A loss had no effect in T21 iPSCs or megakaryocytes with wtGATA1. These surprising results suggest that DYRK1A and GATA1 may synergistically restrain megakaryocyte proliferation in T21 and that DYRK1A inhibition may not be a therapeutic option for GATA1s-associated leukemias.
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- 2023
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29. Generation of CHOPi-008-B, a euploid iPSC line from a patient with Trisomy 21 and a GATA1 mutation.
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Takasaki K, Kumar SS, Gagne A, French DL, and Chou ST
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- Infant, Newborn, Humans, Mutation genetics, Genomic Instability, Trisomy, GATA1 Transcription Factor genetics, Down Syndrome genetics, Leukemia, Megakaryoblastic, Acute genetics, Induced Pluripotent Stem Cells
- Abstract
Transient myeloproliferative disorder (TMD) is a pre-leukemic condition that occurs only in neonates with Trisomy 21 (T21), and is attributed to a genetic interaction between the third copy of chromosome 21 (HSA21) and a mutation in the transcription factor GATA1 that results in a truncated protein (GATA1s). We generated a euploid iPSC line with a GATA1s mutation that is isogenic to a previously published pair of T21 lines with and without a GATA1 mutation. The line was characterized for pluripotency, differentiation potential, and genomic stability. This line is a valuable isogenic control for studying the T21 hematopoietic phenotype., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Editorial board of Stem Cell Research - D.L.F., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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30. Involvement of Diverse Populations in Transfusion Medicine Research.
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Miller YM, Bakhtary S, Chou ST, Hailu B, Reik RA, Richard RH, Spencer BR, Witherspoon R, and Delaney M
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- Humans, Transfusion Medicine, Biomedical Research trends, Diversity, Equity, Inclusion
- Abstract
Communities of color and diverse communities (eg, race, socioeconomic status, language, sexual orientation etc.) have not been recruited and enrolled equitably to participate in research studies in transfusion medicine. The exclusion of diverse communities in transfusion research can lead to health disparities lack of access to approved therapeutics and unequal allocation of interventions, resulting in missed opportunities to optimize health for individuals and communities. Involvement of diverse populations in research goes beyond inclusion as research subjects. Strategies should include specific studies on health conditions of importance to diverse communities with stable funding sources and specific funding announcements to develop projects led by diverse researchers, mentorship of diverse researchers, and openness to various ways of communicating research plans. Qualitative approaches and interdisciplinary collaboration should be supported to enhance inclusivity., Competing Interests: Declaration of Competing Interest In regard to submission of the manuscript, Involvement of Diverse Populations in Transfusion Medicine Research, none of the authors identified conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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31. Proinflammatory state promotes red blood cell alloimmunization in pediatric patients with sickle cell disease.
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Zheng Y, Gossett JM, Chen PL, Barton M, Ryan M, Yu J, Kang G, Hankins JS, and Chou ST
- Subjects
- Humans, Child, Isoantibodies, Erythrocytes, Blood Transfusion, Anemia, Sickle Cell, Anemia, Hemolytic, Autoimmune
- Abstract
We examined risk factors for red blood cell (RBC) alloimmunization in pediatric patients with sickle cell disease, focusing on the recipients' inflammatory state at the time of transfusion and anti-inflammatory role of hydroxyurea (HU). Among 471 participants, 55 (11.70%) participants were alloimmunized and formed 59 alloantibodies and 17 autoantibodies with an alloimmunization rate of 0.36 alloantibodies per 100 units. Analysis of 27 participants in whom alloantibodies were formed with specificities showed 23.8% (30/126) of units transfused during a proinflammatory event resulting in alloantibody formation compared with 2.8% (27/952) of units transfused at steady state. Therefore, transfusion during proinflammatory events increased the risk for alloimmunization (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.64-10.85; P = .003). Further analysis of all the 471 participants showed that alloimmunization of patients who received episodic transfusion, mostly during proinflammatory events, was not reduced with HU therapy (OR, 6.52; 95% CI, 0.85-49.77; P = .071), HU therapy duration (OR, 1.13; 95% CI, 0.997-1.28; P = .056), or HU dose (OR, 1.06; 95% CI, 0.96-1.16; P = .242). The analysis also identified high transfusion burden (OR, 1.02; 95% CI, 1.003-1.04; P = .020) and hemoglobin S (HbSS) and HbSβ0-thalassemia genotypes (OR, 11.22, 95% CI, 1.51-83.38; P = .018) as additional risk factors for alloimmunization. In conclusion, the inflammatory state of transfusion recipients affects the risk of RBC alloimmunization, which is not modified by HU therapy. Judicious use of transfusion during proinflammatory events is critical for preventing alloimmunization., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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32. Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis.
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Wilken MB, Fonar G, Nations C, Pavani G, Tsao V, Garifallou J, Tober J, Bennett L, Maguire JA, Gagne A, Okoli N, Gadue P, Chou ST, Speck NA, French DL, and Thom CS
- Abstract
Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 ( TPM1 ) with human blood trait variation. Prior work suggested that TPM1 regulated blood cell formation in vitro, but it was unclear how or when TPM1 affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, TPM1 knockout was found to augment developmental cell state transitions, as well as TNFα and GTPase signaling pathways, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses showed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects of TPM1 on developmental hematopoiesis.
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- 2023
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33. Generation of a human Tropomyosin 1 knockout iPSC line.
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Wilken MB, Maguire JA, Dungan LV, Gagne A, Osorio-Quintero C, Waxman EA, Chou ST, Gadue P, French DL, and Thom CS
- Subjects
- Humans, Cell Line, Tumor, Tropomyosin genetics, Tropomyosin metabolism, Induced Pluripotent Stem Cells metabolism
- Abstract
The CHOPWT17_TPM1KOc28 iPSC line was generated to interrogate the functions of Tropomyosin 1 (TPM1) in primary human cell development. This line was reprogrammed from a previously published wild type control iPSC line., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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34. Author Correction: HIC2 controls developmental hemoglobin switching by repressing BCL11A transcription.
- Author
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Huang P, Peslak SA, Ren R, Khandros E, Qin K, Keller CA, Giardine B, Bell HW, Lan X, Sharma M, Horton JR, Abdulmalik O, Chou ST, Shi J, Crossley M, Hardison RC, Cheng X, and Blobel GA
- Published
- 2023
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35. In vivo hematopoietic stem cell modification by mRNA delivery.
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Breda L, Papp TE, Triebwasser MP, Yadegari A, Fedorky MT, Tanaka N, Abdulmalik O, Pavani G, Wang Y, Grupp SA, Chou ST, Ni H, Mui BL, Tam YK, Weissman D, Rivella S, and Parhiz H
- Subjects
- Hematopoietic Stem Cell Transplantation, Animals, Humans, Mice, Gene Editing methods, Hematopoietic Stem Cells metabolism, Proto-Oncogene Proteins c-kit genetics, RNA, Messenger genetics
- Abstract
Hematopoietic stem cells (HSCs) are the source of all blood cells over an individual's lifetime. Diseased HSCs can be replaced with gene-engineered or healthy HSCs through HSC transplantation (HSCT). However, current protocols carry major side effects and have limited access. We developed CD117/LNP-messenger RNA (mRNA), a lipid nanoparticle (LNP) that encapsulates mRNA and is targeted to the stem cell factor receptor (CD117) on HSCs. Delivery of the anti-human CD117/LNP-based editing system yielded near-complete correction of hematopoietic sickle cells. Furthermore, in vivo delivery of pro-apoptotic PUMA (p53 up-regulated modulator of apoptosis) mRNA with CD117/LNP affected HSC function and permitted nongenotoxic conditioning for HSCT. The ability to target HSCs in vivo offers a nongenotoxic conditioning regimen for HSCT, and this platform could be the basis of in vivo genome editing to cure genetic disorders, which would abrogate the need for HSCT.
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- 2023
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36. Correlation between facial asymmetry of skeletal class III jaw relationship and morphology of the temporomandibular joint: A cone beam computed tomography study.
- Author
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Chou ST, Wang JL, Chen SC, Pan CY, Chen CM, and Tseng YC
- Abstract
Background/purpose: Facial asymmetry is a common dentofacial deformity especially in skeletal Class III jaw relation. The purpose of this study was to evaluate the condylefossa relationship of Taiwanese people in skeletal Class III jaw relation with or without facial asymmetry by CBCT image., Materials and Methods: CBCT images were collected from Kaohsiung Medical University Hospital and then divided into symmetric Class III group (Menton [Mn] deviation ≦ 4 mm) and asymmetric Class III group (Menton [Mn] deviation > 4 mm). Maxilla deviation, upper and lower dental midline deviation, joint space, condylar axial angle and condylar volume was measured. Independent t test was used for comparison between groups, and paired t test was applied for comparison between both condyles within each group. The Pearson correlation coefficient was used to analyze the correlation between skeletal midline deviations and joint morphology., Results: No significant difference was found in joint space between groups or between sides within each group, but we can find a significant difference in axial condylar angle easurement which was greater on the non-deviation side of condyle. Significant lesser condylar volume was also found on the deviation side in asymmetric group. There had a significant positive correlation between Mn point deviation, geometric center difference and condylar volume ratio., Conclusion: These results demonstrated that in the side with greater mandibular growth potential, the axis rotation in axial plane would be greater. In the side with lesser mandibular growth potential, the total condyle volume would be lesser, even though with large variation., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)
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- 2023
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37. Transfusion therapy for sickle cell disease: what's new?
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Chou ST, Hendrickson JE, and Fasano RM
- Subjects
- Humans, Blood Transfusion, Anemia, Sickle Cell therapy
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- 2023
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38. Variant RHD alleles and Rh immunization in patients with sickle cell disease.
- Author
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Takasaki K, Friedman DF, Uter S, Vege S, Westhoff CM, and Chou ST
- Subjects
- Humans, Alleles, Blood Transfusion, Genotype, Immunization, Phenotype, Rh-Hr Blood-Group System genetics, Anemia, Sickle Cell genetics, Anemia, Sickle Cell therapy
- Abstract
RH diversity among patients and donors contributes to Rh immunization despite serologic Rh-matched red cell transfusions. Anti-D can occur in D+ patients with RHD variants that encode partial D antigens. Anti-D has also been reported in patients with conventional RHD transfused primarily with units from Black donors who frequently have variant RHD. We report 48 anti-D in 690 D+ transfused individuals with sickle cell disease, categorized here as expressing conventional D, partial D or D antigen encoded by RHD*DAU0. Anti-D formed in a greater proportion of individuals with partial D, occurred after fewer D+ unit exposures, and remained detectable for longer than for those in the other categories. Among all anti-D, 13 had clinical or laboratory evidence of poor transfused red cell survival. Most individuals with anti-D were chronically transfused, including 32 with conventional RHD who required an average of 62 D- units/year following anti-D. Our findings suggest that patients with partial D may benefit from prophylactic D- or RH genotype-matched transfusions to prevent anti-D. Future studies should investigate whether RH genotype-matched transfusions can improve use of valuable donations from Black donors, reduce D immunization and minimize transfusion of D- units to D+ individuals with conventional RHD or DAU0 alleles., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2023
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39. Generation of 2 isogenic clones from a patient with Trisomy 21 and a GATA1 mutation.
- Author
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Takasaki K, Kumar SS, Gagne A, French DL, and Chou ST
- Subjects
- Infant, Newborn, Humans, Mutation genetics, Trisomy, GATA1 Transcription Factor genetics, Down Syndrome genetics, Leukemia, Megakaryoblastic, Acute genetics, Myeloproliferative Disorders genetics
- Abstract
Trisomy 21 (T21), or Down Syndrome (DS), is a common chromosomal disorder resulting from a third copy of chromosome 21 (HSA21). Transient myeloproliferative disorder (TMD) is a pre-leukemic condition that occurs only in neonates with DS and is characterized by a mutation in the transcription factor GATA1 that results in a truncated protein (GATA1s). We generated a pair of isogenic T21 lines derived from a patient with TMD that differ only in GATA1 status. The iPSC lines were characterized for pluripotency, differentiation potential, and genomic stability. These lines are a valuable resource for studying T21 hematopoietic diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Editorial board of Stem Cell Research - DLF, (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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40. Functional characterization of the MyD88 homologs in Strongylocentrotus purpuratus.
- Author
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Chou ST, Lin TM, Yang HY, and Fugmann SD
- Subjects
- Animals, Mammals, Strongylocentrotus purpuratus genetics
- Abstract
Toll-like receptor signaling is an evolutionarily conserved pathway to induce the expression of immune mediators in response to encounters with pathogens. MyD88 is a central adapter connecting the intracellular domain of the receptors to downstream kinases. Here, we conducted a comprehensive assessment of the MyD88 family in an echinoderm, Strongylocentrotus purpuratus. Of five SpMyD88s only two closely related proteins, SpMyD88A and SpMyD88B, are functional in mammalian cell lines as their overexpression facilitates the activation of the downstream transcription factor NF-κB. This requires the presence of the endogenous mammalian MyD88s, and domain swapping indicated that the death domains of S. purpuratus MyD88 are unable to efficiently connect to the respective domains of the vertebrate IRAK kinases. This suggests that the interaction surfaces between the signaling mediators in this conserved signaling pathway are not as conserved as previously thought but were likely shaped and evolved by pathogenic selection over evolutionary timescales., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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41. The left and right differences in sella turcica bridging between sex analyzed by cone-beam computed tomography.
- Author
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Chou ST, Chen CM, Chen PH, Lin YC, and Tseng YC
- Abstract
Competing Interests: The authors have no conflicts of interest relevant to this article.
- Published
- 2023
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42. Condylar and ramus volume in asymmetric and symmetric skeletal class III malocclusion: A cone-beam computed tomography study.
- Author
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Chou ST, Tsai PL, Chen SC, Lin SH, Chen CM, and Tseng YC
- Abstract
Background/purpose: Among the craniofacial structures, the mandible is the only bony structure with movable joints. Each part (including condyle process, coronoid process, and ramus) of mandible would interaction with the muscles and proceed different osteogenesis progress. The objective of this study was to evaluate the mandibles with symmetric and asymmetric skeletal Class III jaw relations by quantifying differences in the condyle process, coronoid process and ramus on CBCT (Cone-beam computer tomography) images. Our hypothesis was that CBCT would reveal no voluminal differences between deviated and non-deviated mandibular segments in asymmetric skeletal Class III., Materials and Methods: CBCT imagines were collected from dental department, KMUH and then divided into symmetric Class III group (Menton deviation < 4mm) and asymmetric Class III group (Menton deviation≧4mm). The mandibular structure would be segmented to ramus, condylar and coronoid process. Each volume was measured. Independent t test was used for comparison between groups, and paired t test was applied for comparison between both segmented parts within each group., Results: Significant differences between deviation and non-deviation sides in the asymmetric group were found in condylar and ramus segments for volumetric quantitative measurements. There has no significant difference in ramus parts between groups. Significant greater condylar volume was found in non-deviation side of asymmetric group., Conclusion: The results demonstrated that in the side with greater mandible growth potential, the condylar and the ramus volume would be greater as well. CBCT is a useful and accurate modality for quantification and evaluation of mandibular asymmetry., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)
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- 2023
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43. National Blood Foundation 2021 Research and Development summit: Discovery, innovation, and challenges in advancing blood and biotherapies.
- Author
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Holmberg JA, Henry SM, Burnouf T, Devine D, Marschner S, Boothby TC, Burger SR, Chou ST, Custer B, Blumberg N, Siegel DL, and Spitalnik SL
- Subjects
- Humans, Research, Biological Therapy
- Published
- 2022
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44. The use of pluripotent stem cells to generate diagnostic tools for transfusion medicine.
- Author
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An HH, Gagne AL, Maguire JA, Pavani G, Abdulmalik O, Gadue P, French DL, Westhoff CM, and Chou ST
- Subjects
- Alleles, Humans, Rh-Hr Blood-Group System genetics, Blood Group Antigens genetics, Pluripotent Stem Cells, Transfusion Medicine
- Abstract
Red blood cell (RBC) transfusion is one of the most common medical treatments, with more than 10 million units transfused per year in the United States alone. Alloimmunization to foreign Rh proteins (RhD and RhCE) on donor RBCs remains a challenge for transfusion effectiveness and safety. Alloantibody production disproportionately affects patients with sickle cell disease who frequently receive blood transfusions and exhibit high genetic diversity in the Rh blood group system. With hundreds of RH variants now known, precise identification of Rh antibody targets is hampered by the lack of appropriate reagent RBCs with uncommon Rh antigen phenotypes. Using a combination of human-induced pluripotent stem cell (iPSC) reprogramming and gene editing, we designed a renewable source of cells with unique Rh profiles to facilitate the identification of complex Rh antibodies. We engineered a very rare Rh null iPSC line lacking both RHD and RHCE. By targeting the AAVS1 safe harbor locus in this Rh null background, any combination of RHD or RHCE complementary DNAs could be reintroduced to generate RBCs that express specific Rh antigens such as RhD alone (designated D--), Goa+, or DAK+. The RBCs derived from these iPSCs (iRBCs) are compatible with standard laboratory assays used worldwide and can determine the precise specificity of Rh antibodies in patient plasma. Rh-engineered iRBCs can provide a readily accessible diagnostic tool and guide future efforts to produce an alternative source of rare RBCs for alloimmunized patients., (© 2022 by The American Society of Hematology.)
- Published
- 2022
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45. Adverse events of red blood cell transfusions in patients with sickle cell disease.
- Author
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Rollins MR and Chou ST
- Subjects
- Humans, Erythrocyte Transfusion adverse effects, Erythrocyte Transfusion methods, Blood Safety, Blood Transfusion methods, Anemia, Sickle Cell, Transfusion Reaction complications
- Abstract
Blood transfusion is a common medical intervention for patients with sickle cell disease (SCD) and disease related complications. While patients with SCD are at risk for all transfusion related adverse events defined by the National Healthcare Safety Network (NHSN) Biovigilance Component Hemovigilance Module Surveillance Protocol, they are uniquely susceptible to certain adverse events. This review discusses risk factors, mitigation strategies, and management recommendations for alloimmunization, hemolytic transfusion reactions, hyperviscosity and transfusion-associated iron overload in the context of SCD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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46. HIC2 controls developmental hemoglobin switching by repressing BCL11A transcription.
- Author
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Huang P, Peslak SA, Ren R, Khandros E, Qin K, Keller CA, Giardine B, Bell HW, Lan X, Sharma M, Horton JR, Abdulmalik O, Chou ST, Shi J, Crossley M, Hardison RC, Cheng X, and Blobel GA
- Subjects
- Carrier Proteins genetics, Erythroid Cells metabolism, Humans, Transcription Factors genetics, Transcription Factors metabolism, beta-Globins genetics, beta-Globins metabolism, gamma-Globins genetics, Hemoglobins genetics, Kruppel-Like Transcription Factors metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Tumor Suppressor Proteins metabolism
- Abstract
The fetal-to-adult switch in hemoglobin production is a model of developmental gene control with relevance to the treatment of hemoglobinopathies. The expression of transcription factor BCL11A, which represses fetal β-type globin (HBG) genes in adult erythroid cells, is predominantly controlled at the transcriptional level but the underlying mechanism is unclear. We identify HIC2 as a repressor of BCL11A transcription. HIC2 and BCL11A are reciprocally expressed during development. Forced expression of HIC2 in adult erythroid cells inhibits BCL11A transcription and induces HBG expression. HIC2 binds to erythroid BCL11A enhancers to reduce chromatin accessibility and binding of transcription factor GATA1, diminishing enhancer activity and enhancer-promoter contacts. DNA-binding and crystallography studies reveal direct steric hindrance as one mechanism by which HIC2 inhibits GATA1 binding at a critical BCL11A enhancer. Conversely, loss of HIC2 in fetal erythroblasts increases enhancer accessibility, GATA1 binding and BCL11A transcription. HIC2 emerges as an evolutionarily conserved regulator of hemoglobin switching via developmental control of BCL11A., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
47. Red cell genotyping: Real world use.
- Author
-
Takasaki K and Chou ST
- Subjects
- Genotype, Humans, Real-Time Polymerase Chain Reaction, Blood Grouping and Crossmatching, Genotyping Techniques
- Published
- 2022
- Full Text
- View/download PDF
48. Less pharmacotherapy is more in delirium.
- Author
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Chou ST, Pogach M, and Rock LK
- Subjects
- Humans, Antipsychotic Agents therapeutic use, Delirium drug therapy
- Published
- 2022
- Full Text
- View/download PDF
49. Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells.
- Author
-
Qin K, Huang P, Feng R, Keller CA, Peslak SA, Khandros E, Saari MS, Lan X, Mayuranathan T, Doerfler PA, Abdulmalik O, Giardine B, Chou ST, Shi J, Hardison RC, Weiss MJ, and Blobel GA
- Subjects
- Animals, Carrier Proteins genetics, Erythroid Cells metabolism, Gene Editing, Mice, NFI Transcription Factors genetics, NFI Transcription Factors metabolism, Transcription Factors genetics, beta-Globins genetics, beta-Globins metabolism, Fetal Hemoglobin genetics, Fetal Hemoglobin metabolism, gamma-Globins genetics, gamma-Globins metabolism
- Abstract
The mechanisms by which the fetal-type β-globin-like genes HBG1 and HBG2 are silenced in adult erythroid precursor cells remain a fundamental question in human biology and have therapeutic relevance to sickle cell disease and β-thalassemia. Here, we identify via a CRISPR-Cas9 genetic screen two members of the NFI transcription factor family-NFIA and NFIX-as HBG1/2 repressors. NFIA and NFIX are expressed at elevated levels in adult erythroid cells compared with fetal cells, and function cooperatively to repress HBG1/2 in cultured cells and in human-to-mouse xenotransplants. Genomic profiling, genome editing and DNA binding assays demonstrate that the potent concerted activity of NFIA and NFIX is explained in part by their ability to stimulate the expression of BCL11A, a known silencer of the HBG1/2 genes, and in part by directly repressing the HBG1/2 genes. Thus, NFI factors emerge as versatile regulators of the fetal-to-adult switch in β-globin production., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
50. Publisher Correction: Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells.
- Author
-
Qin K, Huang P, Feng R, Keller CA, Peslak SA, Khandros E, Saari MS, Lan X, Mayuranathan T, Doerfler PA, Abdulmalik O, Giardine B, Chou ST, Shi J, Hardison RC, Weiss MJ, and Blobel GA
- Published
- 2022
- Full Text
- View/download PDF
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