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141 results on '"Ghosheh, Yanal"'

1. Human circulating CD24hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease

Author

Pattarabanjird, Tanyaporn, Nguyen, Anh Tram, McSkimming, Chantel, Dinh, Huy Q., Marshall, Melissa A., Ghosheh, Yanal, Gulati, Rishab, Durant, Chistopher, Vallejo, Jenifer, Saigusa, Ryosuke, Drago, Fabrizio, Guy, Thomas V., Premo, Katherine, Taylor, Angela M., Paul, Soumen, Kundu, Bijoy, Berr, Stuart, Gonen, Ayelet, Tsimikas, Sotirios, Miller, Yury, Pillai, Shiv, Ley, Klaus, Hedrick, Catherine C., and McNamara, Coleen A.

Published
2023
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3. Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production

Author

Orecchioni, Marco, Kobiyama, Kouji, Winkels, Holger, Ghosheh, Yanal, McArdle, Sara, Mikulski, Zbigniew, Kiosses, William B, Fan, Zhichao, Wen, Lai, Jung, Yunmin, Roy, Payel, Ali, Amal J, Miyamoto, Yukiko, Mangan, Matthew, Makings, Jeffrey, Wang, Zhihao, Denn, Angela, Vallejo, Jenifer, Owens, Michaela, Durant, Christopher P, Braumann, Simon, Mader, Navid, Li, Lin, Matsunami, Hiroaki, Eckmann, Lars, Latz, Eicke, Wang, Zeneng, Hazen, Stanley L, and Ley, Klaus

Subjects
Atherosclerosis, Cardiovascular, Neurosciences, Aging, 2.1 Biological and endogenous factors, Aetiology, Adult, Aldehydes, Animals, Aorta, Humans, Inflammasomes, Interleukin-1, Interleukin-1alpha, Interleukin-1beta, Lipid Peroxidation, Macrophages, Mice, Mice, Inbred C57BL, Middle Aged, NLR Family, Pyrin Domain-Containing 3 Protein, Oxidative Stress, Receptors, Odorant, Signal Transduction, General Science & Technology
Abstract

Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled chemoreceptors that have a central role in detecting odorants and the sense of smell. We found that mouse vascular macrophages express the olfactory receptor Olfr2 and all associated trafficking and signaling molecules. Olfr2 detects the compound octanal, which activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome and induces interleukin-1β secretion in human and mouse macrophages. We found that human and mouse blood plasma contains octanal, a product of lipid peroxidation, at concentrations sufficient to activate Olfr2 and the human ortholog olfactory receptor 6A2 (OR6A2). Boosting octanal levels exacerbated atherosclerosis, whereas genetic targeting of Olfr2 in mice significantly reduced atherosclerotic plaques. Our findings suggest that inhibiting OR6A2 may provide a promising strategy to prevent and treat atherosclerosis.

Published
2022

4. Author Correction: Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Suthahar, Sujit Silas Armstrong, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Developmental Biology, Biological sciences
Abstract

The original article [1] contained significant errors in Fig 1A which necessitated correction; the figure has since been updated to the corrected version.

Published
2022

5. Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Armstrong Suthahar, Sujit Silas, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus

Subjects
Biological Sciences, Bioinformatics and Computational Biology, HIV/AIDS, Genetics, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Female, Flow Cytometry, Gene Expression Profiling, HIV Infections, Humans, Leukocytes, Mononuclear, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome, CVD, HIV, scRNA-seq, Transcriptomes, Antibodies, Human, Developmental Biology, Biological sciences
Abstract

BackgroundCryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.ResultsAmong 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.ConclusionsIn conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Published
2022

6. Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells

Author

Saigusa, Ryosuke, Vallejo, Jenifer, Gulati, Rishab, Suthahar, Sujit Silas Armstrong, Suryawanshi, Vasantika, Alimadadi, Ahmad, Makings, Jeffrey, Durant, Christopher P, Freuchet, Antoine, Roy, Payel, Ghosheh, Yanal, Pandori, William, Pattarabanjird, Tanyaporn, Drago, Fabrizio, Taylor, Angela, McNamara, Coleen A, Shemesh, Avishai, Lanier, Lewis L, Hedrick, Catherine C, and Ley, Klaus

Subjects
Genetics, Atherosclerosis, Human Genome, Diabetes, Cardiovascular, Clinical Research, Heart Disease - Coronary Heart Disease, Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Good Health and Well Being, CD4-Positive T-Lymphocytes, Coronary Angiography, Coronary Artery Disease, Diabetes Mellitus, Female, Humans, Leukocytes, Mononuclear, Male, Sex Characteristics, Single-Cell Analysis, coronary artery disease, diabetes, CITE-Seq, scRNA-Seq, PBMC, Other Chemical Sciences, Other Biological Sciences, Chemical Physics
Abstract

Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T cells as drivers and modifiers of CAD. CD4+ T cells are commonly found in atherosclerotic plaques. We aimed to understand the relationship of CAD with sex and DM by single-cell RNA (scRNA-Seq) and antibody sequencing (CITE-Seq) of CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by scRNA-Seq combined with 49 surface markers (CITE-Seq). CAD severity was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD-. Four pairs of groups were matched for clinical and demographic parameters. To test how sex and DM changed cell proportions and gene expression, we compared matched groups of men and women, as well as diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 16 women and 45 men with and without coronary artery disease and with and without DM. We identified 16 clusters in CD4+ T cells. The proportion of cells in CD4+ effector memory cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. This same cluster, CD4T8, was significantly decreased in female participants, along with two other CD4+ T cell clusters. In CD4+ T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. We conclude that (1) CAD and DM are clearly reflected in PBMC transcriptomes, and (2) significant differences exist between women and men and (3) between subjects with DM and non-DM.

Published
2022

7. Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing

Author

Yuan, Baolei, Zhou, Xuan, Suzuki, Keiichiro, Ramos-Mandujano, Gerardo, Wang, Mengge, Tehseen, Muhammad, Cortés-Medina, Lorena V, Moresco, James J, Dunn, Sarah, Hernandez-Benitez, Reyna, Hishida, Tomoaki, Kim, Na Young, Andijani, Manal M, Bi, Chongwei, Ku, Manching, Takahashi, Yuta, Xu, Jinna, Qiu, Jinsong, Huang, Ling, Benner, Christopher, Aizawa, Emi, Qu, Jing, Liu, Guang-Hui, Li, Zhongwei, Yi, Fei, Ghosheh, Yanal, Shao, Changwei, Shokhirev, Maxim, Comoli, Patrizia, Frassoni, Francesco, Yates, John R, Fu, Xiang-Dong, Esteban, Concepcion Rodriguez, Hamdan, Samir, Izpisua Belmonte, Juan Carlos, and Li, Mo

Subjects
Rare Diseases, Human Genome, Genetics, Generic health relevance, Alternative Splicing, Cell Nucleus, Humans, RNA Polymerase II, RNA Splicing Factors, RNA-Binding Proteins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein
Abstract

The diverse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Loss of WASP binding to splicing factor gene promoters frequently leads to aberrant epigenetic activation. WASP interacts with dozens of nuclear speckle constituents and constrains SRSF2 mobility. Using an optogenetic system, we showed that WASP forms phase-separated condensates that encompasses SRSF2, nascent RNA and active Pol II. The role of WASP in gene body condensates is corroborated by ChIPseq and RIPseq. Together our data reveal that WASP is a nexus regulator of RNA splicing that controls the transcription of splicing factors epigenetically and the dynamics of the splicing machinery through liquid-liquid phase separation.

Published
2022

8. Author Correction: Human circulating CD24hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease

Author

Pattarabanjird, Tanyaporn, Nguyen, Anh Tram, McSkimming, Chantel, Dinh, Huy Q., Marshall, Melissa A., Ghosheh, Yanal, Gulati, Rishab, Durant, Chistopher, Vallejo, Jenifer, Saigusa, Ryosuke, Drago, Fabrizio, Guy, Thomas V., Premo, Katherine, Taylor, Angela M., Paul, Soumen, Kundu, Bijoy, Berr, Stuart, Gonen, Ayelet, Tsimikas, Sotirios, Miller, Yury, Pillai, Shiv, Ley, Klaus, Hedrick, Catherine C., and McNamara, Coleen A.

Published
2023
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9. Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain

Author

Navia-Pelaez, Juliana M, Choi, Soo-Ho, dos Santos Aggum Capettini, Luciano, Xia, Yining, Gonen, Ayelet, Agatisa-Boyle, Colin, Delay, Lauriane, dos Santos, Gilson Gonçalves, Catroli, Glaucilene F, Kim, Jungsu, Lu, Jenny W, Saylor, Benjamin, Winkels, Holger, Durant, Christopher P, Ghosheh, Yanal, Beaton, Graham, Ley, Klaus, Kufareva, Irina, Corr, Maripat, Yaksh, Tony L, and Miller, Yury I

Subjects
Pain Research, Neurodegenerative, Neurosciences, Peripheral Neuropathy, Genetics, Chronic Pain, Aetiology, 2.1 Biological and endogenous factors, Neurological, ATP Binding Cassette Transporter 1, ATP Binding Cassette Transporter, Subfamily G, Member 1, Animals, Biological Transport, Cell Line, Cholesterol, HEK293 Cells, Humans, Inflammation, Male, Membrane Microdomains, Mice, Mice, Inbred C57BL, Microglia, Neuralgia, Protein Binding, Signal Transduction, Spinal Cord, Medical and Health Sciences, Immunology
Abstract

Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1-deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling the TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.

Published
2021

11. Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease

Author

Saigusa, Ryosuke, Roy, Payel, Freuchet, Antoine, Gulati, Rishab, Ghosheh, Yanal, Armstrong Suthahar, Sujit Silas, Durant, Christopher P., Hanna, David B., Kiosses, William B., Orecchioni, Marco, Wen, Lai, Wu, Runpei, Kuniholm, Mark H., Landay, Alan L., Anastos, Kathryn, Tien, Phyllis C., Gange, Stephen J., Kassaye, Seble, Vallejo, Jenifer, Hedrick, Catherine C., Kwok, William W., Sette, Alessandro, Hodis, Howard N., Kaplan, Robert C., and Ley, Klaus

Published
2022
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12. Author Correction: Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing

Author

Yuan, Baolei, Zhou, Xuan, Suzuki, Keiichiro, Ramos-Mandujano, Gerardo, Wang, Mengge, Tehseen, Muhammad, Cortés-Medina, Lorena V., Moresco, James J., Dunn, Sarah, Hernandez-Benitez, Reyna, Hishida, Tomoaki, Kim, Na Young, Andijani, Manal M., Bi, Chongwei, Ku, Manching, Takahashi, Yuta, Xu, Jinna, Qiu, Jinsong, Huang, Ling, Benner, Christopher, Aizawa, Emi, Qu, Jing, Liu, Guang-Hui, Li, Zhongwei, Yi, Fei, Ghosheh, Yanal, Shao, Changwei, Shokhirev, Maxim, Comoli, Patrizia, Frassoni, Francesco, Yates, III, John R., Fu, Xiang-Dong, Esteban, Concepcion Rodriguez, Hamdan, Samir, Izpisua Belmonte, Juan Carlos, and Li, Mo

Published
2022
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14. High-Affinity Bent β2-Integrin Molecules in Arresting Neutrophils Face Each Other through Binding to ICAMs In cis

Author

Fan, Zhichao, Kiosses, William Bill, Sun, Hao, Orecchioni, Marco, Ghosheh, Yanal, Zajonc, Dirk M, Arnaout, M Amin, Gutierrez, Edgar, Groisman, Alex, Ginsberg, Mark H, and Ley, Klaus

Subjects
Biochemistry and Cell Biology, Biological Sciences, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, CD18 Antigens, Cell Adhesion Molecules, Humans, Neutrophils, Protein Binding, STORM, TIRF, human, integrin, integrin activation, molecular modeling, neutrophil, superresolution, Medical Physiology, Biological sciences
Abstract

Leukocyte adhesion requires β2-integrin activation. Resting integrins exist in a bent-closed conformation-i.e., not extended (E-) and not high affinity (H-)-unable to bind ligand. Fully activated E+H+ integrin binds intercellular adhesion molecules (ICAMs) expressed on the opposing cell in trans. E-H- transitions to E+H+ through E+H- or through E-H+, which binds to ICAMs on the same cell in cis. Spatial patterning of activated integrins is thought to be required for effective arrest, but no high-resolution cell surface localization maps of activated integrins exist. Here, we developed Super-STORM by combining super-resolution microscopy with molecular modeling to precisely localize activated integrin molecules and identify the molecular patterns of activated integrins on primary human neutrophils. At the time of neutrophil arrest, E-H+ integrins face each other to form oriented (non-random) nanoclusters. To address the mechanism causing this pattern, we blocked integrin binding to ICAMs in cis, which significantly relieved the face-to-face orientation.

Published
2019

15. Single-cell profiling of CD11c+ B cells in atherosclerosis

Author

Pattarabanjird, Tanyaporn, primary, Srikakulapu, Prasad, additional, Ransegnola, Brett, additional, Marshall, Melissa A., additional, Ghosheh, Yanal, additional, Gulati, Rishab, additional, Durant, Chistopher, additional, Drago, Fabrizio, additional, Taylor, Angela M., additional, Ley, Klaus, additional, and McNamara, Coleen A., additional

Published
2024
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16. Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease

Author

Iqneibi, Shahad, primary, Saigusa, Ryosuke, additional, Khan, Amir, additional, Oliaeimotlagh, Mohammad, additional, Armstrong Suthahar, Sujit Silas, additional, Kumar, Sunil, additional, Alimadadi, Ahmad, additional, Durant, Christopher P., additional, Ghosheh, Yanal, additional, McNamara, Coleen A., additional, Hedrick, Catherine C., additional, and Ley, Klaus, additional

Published
2023
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17. HIV infection and cardiovascular disease have both shared and distinct monocyte gene expression features: Women’s Interagency HIV study

Author

Lin, Juan, primary, Ehinger, Erik, additional, Hanna, David B., additional, Qi, Qibin, additional, Wang, Tao, additional, Ghosheh, Yanal, additional, Mueller, Karin, additional, Anastos, Kathryn, additional, Lazar, Jason M., additional, Mack, Wendy J., additional, Tien, Phyllis C., additional, Berman, Joan W., additional, Cohen, Mardge H., additional, Ofotokun, Igho, additional, Gange, Stephen, additional, Liu, Chenglong, additional, Heath, Sonya L., additional, Tracy, Russell P., additional, Hodis, Howard N., additional, Landay, Alan L., additional, Ley, Klaus, additional, and Kaplan, Robert C., additional

Published
2023
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18. Single cell transcriptomic changes of CD8T cells in male and female patients with coronary artery disease and diabetes

Author

Iqneibi, Shahad, primary, Saigusa, Ryosuke, additional, Suthahar, Sujit Silas Armstrong, additional, Khan, Amir, additional, Oliaeimotlagh, Mohammad, additional, Gulati, Rishab, additional, Suryawanshi, Vasantika, additional, Alimadadi, Ahmad, additional, Pandori, William, additional, Makings, Jeff, additional, Durant, Christopher, additional, Ghosheh, Yanal, additional, Durant, Fabrizio, additional, McNamara, Coleen, additional, Shemesh, Avishai, additional, Lanier, Lewis L, additional, Hedrick, Catherine, additional, and Ley, Klaus, additional

Published
2023
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19. Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B100–Reactive CD4+ T-Regulatory Cells

Author

Wolf, Dennis, Gerhardt, Teresa, Winkels, Holger, Michel, Nathaly Anto, Pramod, Akula Bala, Ghosheh, Yanal, Brunel, Simon, Buscher, Konrad, Miller, Jacqueline, McArdle, Sara, Baas, Livia, Kobiyama, Kouji, Vassallo, Melanie, Ehinger, Erik, Dileepan, Thamotharampillai, Ali, Amal, Schell, Maximilian, Mikulski, Zbigniew, Sidler, Daniel, Kimura, Takayuki, Sheng, Xia, Horstmann, Hauke, Hansen, Sophie, Mitre, Lucia Sol, Stachon, Peter, Hilgendorf, Ingo, Gaddis, Dalia E., Hedrick, Catherine, Benedict, Chris A., Peters, Bjoern, Zirlik, Andreas, Sette, Alessandro, and Ley, Klaus

Published
2020
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22. Single-cell transcriptomes and T cell receptors of vaccine-expanded apolipoprotein B-specific T cells

Author

Nettersheim, Felix Sebastian, primary, Ghosheh, Yanal, additional, Winkels, Holger, additional, Kobiyama, Kouji, additional, Durant, Christopher, additional, Armstrong, Sujit Silas, additional, Brunel, Simon, additional, Roy, Payel, additional, Dileepan, Thamotharampillai, additional, Jenkins, Marc K., additional, Zajonc, Dirk M., additional, and Ley, Klaus, additional

Published
2023
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24. Sex differences in coronary artery disease and diabetes revealed by scRNA-Seq and CITE-Seq of human CD4+ T cells

Author

Saigusa, Ryosuke, primary, Vallejo, Jenifer, additional, Gulati, Rishab, additional, Suthahar, Sujit Silas Armstrong, additional, Suryawanshi, Vasantika, additional, Alimadadi, Ahmad, additional, Markings, Jeff, additional, Durant, Christopher P., additional, Freuchet, Antoine, additional, Roy, Payel, additional, Ghosheh, Yanal, additional, Pandori, William, additional, Pattarabanjird, Tanyaporn, additional, Drago, Fabrizio, additional, McNamara, Coleen A., additional, Shemesh, Avishai, additional, Lanier, Lewis L., additional, Hedrick, Catherine C., additional, and Ley, Klaus, additional

Published
2022
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26. Additional file 1 of Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Armstrong Suthahar, Sujit Silas, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P., Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B., Landay, Alan L., Tracy, Russell P., Lazar, Jason M., Mack, Wendy J., Weber, Kathleen M., Adimora, Adaora A., Hodis, Howard N., Tien, Phyllis C., Ofotokun, Igho, Heath, Sonya L., Shemesh, Avishai, McNamara, Coleen A., Lanier, Lewis L., Hedrick, Catherine C., Kaplan, Robert C., and Ley, Klaus

Abstract

Additional file 1: Supplementary Figures and Tables. Figure S1. (Related to Figure 1). Design of the study comparison between study participants. Figure S2. (Related to Figure 1). (A) Ridgeline plots of the unthresholded expressions of all the 40 surface markers for each main cell types. (B) Age projection (below and above median) onto CM, INT, NCM, CD4+ T cells and CD8+ T cell UMAPs. Figure S3. (Related to Figure 5). Dotplots of DEG for disease types for subsets. Table S1. Reagents. Table S2. The cell viability of each frozen PBMC tube. Table S3. List of 40 titrated oligonucleotide-tagged monoclonal antibodies. Table S4. List of selected genes included in the custom panel. Table S5. Threshold values of each antibody. Table S6. Antibodies not used for cell clustering. Table S7. Number of Cells in each of the clusters. Table S8. Significantly differentially expressed genes for each cell type (A-E). Table S9. Number of Cells for each participant. Table S10. Non-negative Spearman correlation between antibody and gene in each cell type.

Published
2022
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27. Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease

Author

Pattarabanjird, Tanyaporn, primary, Wilson, Jeffrey M., additional, Erickson, Loren D., additional, Workman, Lisa J., additional, Qiao, Hui, additional, Ghosheh, Yanal, additional, Gulati, Rishab, additional, Durant, Chistopher, additional, Vallejo, Jenifer, additional, Saigusa, Ryosuke, additional, Platts-Mills, Thomas A. E., additional, Taylor, Angela M., additional, Ley, Klaus, additional, and McNamara, Coleen A., additional

Published
2022
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28. Thymus-Derived CD4+CD8+ Cells Reside in Mediastinal Adipose Tissue and the Aortic Arch

Author

Winkels, Holger, primary, Ghosheh, Yanal, additional, Kobiyama, Kouji, additional, Kiosses, William B., additional, Orecchioni, Marco, additional, Ehinger, Erik, additional, Suryawanshi, Vasantika, additional, Herrera-De La Mata, Sara, additional, Marchovecchio, Paola, additional, Riffelmacher, Thomas, additional, Thiault, Nicolas, additional, Kronenberg, Mitchell, additional, Wolf, Dennis, additional, Seumois, Gregory, additional, Vijayanand, Pandurangan, additional, and Ley, Klaus, additional

Published
2021
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29. Abstract MP04: Single Cell Profiling Identifies IgM To MDA-LDL Producing Human B Cells And Atheroprotective Role Of CD24

Author

Pattarabanjird, Tanyaporn, primary, Nguyen, Anh, additional, McSkimming, Chantel, additional, Dinh, Huy, additional, Marshall, Melissa, additional, Ghosheh, Yanal, additional, Durant, Chirstopher, additional, Vallejo, Jenifer, additional, Gulati, Rishab, additional, Saigusa, Ryosuke, additional, Drago, Fabrizio, additional, Taylor, Angela, additional, Gonen, Ayelet, additional, Tsimikas, Sotirios, additional, Miller, Yury I, additional, Ley, Klaus F, additional, Hedrick, Catherine C, additional, and McNamara, Coleen A, additional

Published
2021
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30. Partial Inhibition of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase-3 (PFKFB3) Enzyme in Myeloid Cells Does Not Affect Atherosclerosis

Author

Tillie, Renée J. H. A., primary, De Bruijn, Jenny, additional, Perales-Patón, Javier, additional, Temmerman, Lieve, additional, Ghosheh, Yanal, additional, Van Kuijk, Kim, additional, Gijbels, Marion J., additional, Carmeliet, Peter, additional, Ley, Klaus, additional, Saez-Rodriguez, Julio, additional, and Sluimer, Judith C., additional

Published
2021
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31. Single cell profiling identifies IgMMDA-LDL-producing human B cells and a novel role for CD24

Author

Pattarabanjird, Tanyaporn, primary, Nguyen, Anh Tram, additional, McSkimming, Chantel, additional, Dinh, Huy, additional, Marshall, Melissa A, additional, Ghosheh, Yanal, additional, Gulati, Rishab, additional, Durant, Chistopher, additional, Vallejo, Jenifer, additional, Saigusa, Ryosuke, additional, Drago, Fabrizio, additional, Taylor, Angela M, additional, Tsimikas, Sotirios, additional, Miller, Yury, additional, Ley, Klaus, additional, Hedrick, Catherine C., additional, and McNamara, Coleen A, additional

Published
2021
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32. Identification of human exTregcells as CD16+CD56+cytotoxic CD4+T cells

Author

Freuchet, Antoine, Roy, Payel, Armstrong, Sujit Silas, Oliaeimotlagh, Mohammad, Kumar, Sunil, Orecchioni, Marco, Ali, Amal J., Khan, Amir, Makings, Jeffrey, Lyu, Qingkang, Winkels, Holger, Wang, Erpei, Durant, Christopher, Ghosheh, Yanal, Gulati, Rishab, Nettersheim, Felix, and Ley, Klaus

Abstract

In atherosclerosis, some regulatory T (Treg) cells become exTregcells. We crossed inducible Tregand exTregcell lineage-tracker mice (FoxP3eGFP−Cre-ERT2ROSA26CAG-fl-stop-fl-tdTomato) to atherosclerosis-prone Apoe−/−mice, sorted Tregcells and exTregcells and determined their transcriptomes by bulk RNA sequencing (RNA-seq). Genes that were differentially expressed between mouse Tregcells and exTregcells and filtered for their presence in a human single-cell RNA-sequencing (scRNA-seq) panel identified exTregcell signature genes as CST7, NKG7, GZMA, PRF1, TBX21and CCL4. Projecting these genes onto the human scRNA-seq with CITE-seq data identified human exTregcells as CD3+CD4+CD16+CD56+, which was validated by flow cytometry. Bulk RNA-seq of sorted human exTregcells identified them as inflammatory and cytotoxic CD4+T cells that were significantly distinct from both natural killer and Tregcells. DNA sequencing for T cell receptor-β showed clonal expansion of Tregcell CDR3 sequences in exTregcells. Cytotoxicity was functionally demonstrated in cell killing and CD107a degranulation assays, which identifies human exTregcells as cytotoxic CD4+T cells.

Published
2023
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33. Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B 100 –Reactive CD4 + T-Regulatory Cells

Author

Wolf, Dennis, primary, Gerhardt, Teresa, additional, Winkels, Holger, additional, Michel, Nathaly Anto, additional, Pramod, Akula Bala, additional, Ghosheh, Yanal, additional, Brunel, Simon, additional, Buscher, Konrad, additional, Miller, Jacqueline, additional, McArdle, Sara, additional, Baas, Livia, additional, Kobiyama, Kouji, additional, Vassallo, Melanie, additional, Ehinger, Erik, additional, Dileepan, Thamotharampillai, additional, Ali, Amal, additional, Schell, Maximilian, additional, Mikulski, Zbigniew, additional, Sidler, Daniel, additional, Kimura, Takayuki, additional, Sheng, Xia, additional, Horstmann, Hauke, additional, Hansen, Sophie, additional, Mitre, Lucia Sol, additional, Stachon, Peter, additional, Hilgendorf, Ingo, additional, Gaddis, Dalia E., additional, Hedrick, Catherine, additional, Benedict, Chris A., additional, Peters, Bjoern, additional, Zirlik, Andreas, additional, Sette, Alessandro, additional, and Ley, Klaus, additional

Published
2020
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34. Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, primary, Saigusa, Ryosuke, additional, Gulati, Rishab, additional, Ghosheh, Yanal, additional, Durant, Christopher P., additional, Roy, Payel, additional, Ehinger, Erik, additional, Suryawanshi, Vasantika, additional, Pattarabanjird, Tanyaporn, additional, Padgett, Lindsey E., additional, Olingy, Claire E., additional, Hanna, David B., additional, Landay, Alan L., additional, Tracy, Russell P., additional, Lazar, Jason M., additional, Mack, Wendy J., additional, Weber, Kathleen M., additional, Adimora, Adaora A., additional, Hodis, Howard N., additional, Tien, Phyllis C., additional, Ofotokun, Igho, additional, Heath, Sonya L., additional, Blanco-Dominguez, Rafael, additional, Dinh, Huy Q., additional, Shemesh, Avishai, additional, McNamara, Coleen A., additional, Lanier, Lewis L., additional, Hedrick, Catherine C., additional, Kaplan, Robert C., additional, and Ley, Klaus, additional

Published
2020
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35. Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas

Author

Zernecke, Alma, primary, Winkels, Holger, additional, Cochain, Clément, additional, Williams, Jesse W., additional, Wolf, Dennis, additional, Soehnlein, Oliver, additional, Robbins, Clint S., additional, Monaco, Claudia, additional, Park, Inhye, additional, McNamara, Coleen A., additional, Binder, Christoph J., additional, Cybulsky, Myron I., additional, Scipione, Corey A., additional, Hedrick, Catherine C., additional, Galkina, Elena V., additional, Kyaw, Tin, additional, Ghosheh, Yanal, additional, Dinh, Huy Q., additional, and Ley, Klaus, additional

Published
2020
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36. Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV

Author

Ehinger, Erik, primary, Ghosheh, Yanal, additional, Pramod, Akula Bala, additional, Lin, Juan, additional, Hanna, David B, additional, Mueller, Karin, additional, Durant, Christopher P, additional, Baas, Livia, additional, Qi, Qibin, additional, Wang, Tao, additional, Buscher, Konrad, additional, Anastos, Kathryn, additional, Lazar, Jason M, additional, Mack, Wendy J, additional, Tien, Phyllis C, additional, Cohen, Mardge H, additional, Ofotokun, Igho, additional, Gange, Stephen, additional, Heath, Sonya L, additional, Hodis, Howard N, additional, Tracy, Russell P, additional, Landay, Alan L, additional, Kaplan, Robert C, additional, and Ley, Klaus, additional

Published
2020
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38. CD4 and CD8 double positive T cell progenitors in mediastinal adipose tissue and the aortic arch differentiate to CD4 T cells

Author

Winkels, Holger, primary, Ghosheh, Yanal, additional, Kobiyama, Kouji, additional, Kiosses, William B, additional, Marcovecchio, Paola, additional, Orecchioni, Marco, additional, Wolf, Dennis, additional, Thiault, Nicolas, additional, Seumois, Gregory, additional, Vijayanand, Pandurangan, additional, and Ley, Klaus, additional

Published
2020
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39. Olfactory receptor 2 (Olfr2) and its human ortholog OR6A2 expressed in macrophages drive NLRP3 inflammasome activation and exacerbate atherosclerosis in mice

Author

Orecchioni, Marco, primary, Kobiyama, Kouji, additional, Winkels, Holger, additional, Ghosheh, Yanal, additional, McArdle, Sara, additional, Mikulski, Zbigniew, additional, Fan, Zhichao, additional, Wen, Lai, additional, Jung, Yunmin, additional, Roy, Payel, additional, Myamoto, Yukiko, additional, Matsunami, Hiroaki, additional, Eckmann, Lars, additional, Latz, Eicke, additional, Wang, Zeneng, additional, Hazen, Stanley L, additional, and Ley, Klaus, additional

Published
2020
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40. Abstract P323: HIV- and Subclinical Cardiovascular Disease-specific Transcriptomes in Nonclassical Monocytes: The Women’s Interagency HIV Study

Author

Lin, Juan, primary, Hanna, David B, additional, Qi, Qibin, additional, wang, tao, additional, Mueller, Karin A, additional, Ghosheh, Yanal, additional, Anastos, Kathryn, additional, LAZAR, Jason M, additional, MacK, Wendy, additional, Tien, Phyllis, additional, COHEN, MARDGE, additional, igho, ofotokun, additional, Gange, Stephen, additional, HEATH, SONIA, additional, Tracy, Russell P, additional, Hodis, Howard N, additional, LANDAY, ALAN, additional, Kaplan, Robert, additional, and Ley, Klaus F, additional

Published
2020
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42. Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells

Author

Shuaib, Muhammad, primary, Parsi, Krishna Mohan, additional, Thimma, Manjula, additional, Adroub, Sabir Abdu, additional, Kawaji, Hideya, additional, Seridi, Loqmane, additional, Ghosheh, Yanal, additional, Fort, Alexandre, additional, Fallatah, Bodor, additional, Ravasi, Timothy, additional, Carninci, Piero, additional, and Orlando, Valerio, additional

Published
2019
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43. AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells: Supplemental Data

Author

Shuaib, Muhammad, Parsi, Krishna Mohan, Kawaji, Hideya, Thimma, Manjula, Adroub, Sabir Abdu, Fort, Alexandre, Ghosheh, Yanal, Yamazaki, Tomohiro, Mannen, Taro, Seridi, Loqmane, Fallatah, Bodor, Albawardi, Waad, Ravasi, Timothy, Carninci, Piero, Hirose, Tetsuro, and Orlando, Valerio

Subjects
fungi
Abstract

Aside from their roles in the cytoplasm, RNA-interference components have been reported to localize also in the nucleus of human cells. In particular, AGO1 associates with active chromatin and appears to influence global gene expression. However, the mechanistic aspects remain elusive. Here, we identify AGO1 as a paraspeckle component that in combination with the NEAT1 lncRNA maintains 3D genome architecture. We demonstrate that AGO1 interacts with NEAT1 lncRNA and its depletion affects NEAT1 expression and the formation of paraspeckles. By Hi-C analysis in AGO1 knockdown cells, we observed global changes in chromatin organization, including TADs configuration, and A/B compartment mixing. Consistently, distinct groups of genes located within the differential interacting loci showed altered expression upon AGO1 depletion. NEAT1 knockout cells displayed similar changes in TADs and higher-order A/B compartmentalization. We propose that AGO1 in association with NEAT1 lncRNA can act as a scaffold that bridges chromatin and nuclear bodies to regulate genome organization and gene expression in human cells.

Published
2019
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44. Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV.

Author

Ehinger, Erik, Ghosheh, Yanal, Pramod, Akula Bala, Lin, Juan, Hanna, David B, Mueller, Karin, Durant, Christopher P, Baas, Livia, Qi, Qibin, Wang, Tao, Buscher, Konrad, Anastos, Kathryn, Lazar, Jason M, Mack, Wendy J, Tien, Phyllis C, Cohen, Mardge H, Ofotokun, Igho, Gange, Stephen, Heath, Sonya L, and Hodis, Howard N

Subjects
*MONONUCLEAR leukocytes, *STATINS (Cardiovascular agents), *HIV-positive persons, *HIV infections, *HIV
Abstract

Aims During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability. Methods and results Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women's Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women's Interagency HIV Study and deep-sequenced their mRNA (n  = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV−sCVD−) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production. Conclusion Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD. [ABSTRACT FROM AUTHOR]

Published
2021
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46. AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

Author

Shuaib, Muhammad, primary, Parsi, Krishna Mohan, additional, Kawaji, Hideya, additional, Thimma, Manjula, additional, Adroub, Sabir Abdu, additional, Fort, Alexandre, additional, Ghosheh, Yanal, additional, Yamazaki, Tomohiro, additional, Mannen, Taro, additional, Seridi, Loqmane, additional, Fallatah, Bodor, additional, Albawardi, Waad, additional, Ravasi, Timothy, additional, Carninci, Piero, additional, Hirose, Tetsuro, additional, and Orlando, Valerio, additional

Published
2019
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47. Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B100-Reactive CD4+ T-Regulatory Cells.

Author

Wolf, Dennis, Gerhardt, Teresa, Winkels, Holger, Michel, Nathaly Anto, Pramod, Akula Bala, Ghosheh, Yanal, Brunel, Simon, Buscher, Konrad, Miller, Jacqueline, McArdle, Sara, Baas, Livia, Kobiyama, Kouji, Vassallo, Melanie, Ehinger, Erik, Dileepan, Thamotharampillai, Ali, Amal, Schell, Maximilian, Mikulski, Zbigniew, Sidler, Daniel, and Kimura, Takayuki

Published
2020
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48. Wiskott-Aldrich Syndrome Protein Regulates Nuclear Organization, Alternative Splicing and Cell Proliferation

Author

Li, Mo, primary, Suzuki, Keiichiro, additional, Zhou, Xuan, additional, Yamauchi, Takayoshi, additional, Moresco, James J., additional, Dunn, Sarah, additional, Benitez, Reyna Hernandez-, additional, Hishida, Tomoaki, additional, Kim, Na Young, additional, Andijani, Manal M., additional, Ku, Manching, additional, Takahashi, Yuta, additional, Xu, Jinna, additional, Qiu, Jinsong, additional, Huang, Ling, additional, Benner, Christopher, additional, Aizawa, Emi, additional, Qu, Jing, additional, Liu, Guang-Hui, additional, Li, Zhongwei, additional, Yi, Fei, additional, Bi, Chongwei, additional, Ghosheh, Yanal, additional, Shao, Changwei, additional, Shokhirev, Maxim, additional, Comoli, Patrizia, additional, Frassoni, Francesco, additional, III, John R. Yates, additional, Fu, Xiang-Dong, additional, Esteban, Concepcion Rodriguez, additional, and Belmonte, Juan Carlos Izpisua, additional

Published
2018
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49. Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B100–Reactive CD4+T-Regulatory Cells

Author

Wolf, Dennis, Gerhardt, Teresa, Winkels, Holger, Michel, Nathaly Anto, Pramod, Akula Bala, Ghosheh, Yanal, Brunel, Simon, Buscher, Konrad, Miller, Jacqueline, McArdle, Sara, Baas, Livia, Kobiyama, Kouji, Vassallo, Melanie, Ehinger, Erik, Dileepan, Thamotharampillai, Ali, Amal, Schell, Maximilian, Mikulski, Zbigniew, Sidler, Daniel, Kimura, Takayuki, Sheng, Xia, Horstmann, Hauke, Hansen, Sophie, Mitre, Lucia Sol, Stachon, Peter, Hilgendorf, Ingo, Gaddis, Dalia E., Hedrick, Catherine, Benedict, Chris A., Peters, Bjoern, Zirlik, Andreas, Sette, Alessandro, and Ley, Klaus

Abstract

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Published
2020
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