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4. Human monocyte subtype expression of neuroinflammation- and regeneration-related genes is linked to age and sex.

Author

Tampé, Juliane F., Monni, Emanuela, Palma-Tortosa, Sara, Brogårdh, Emil, Böiers, Charlotta, Lindgren, Arne G., and Kokaia, Zaal

Subjects
SEX (Biology), GENE expression, ISCHEMIC stroke, MONOCYTES, BLOOD testing, NEURODEGENERATION
Abstract

Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of immune cells is implicated in the development and progression of numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Monocytes and monocyte-derived macrophages, being important players in the inflammatory response, significantly influence the aging process and the associated increase in inflammatory disease risk. Ischemic stroke is among age-related diseases where inflammation, particularly monocyte-derived macrophages, plays an important deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences the incidence, presentation, and outcomes of ischemic stroke, reflecting both biological differences between men and women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of genes implicated in stroke-related inflammation and post-stroke tissue regeneration depends on age and sex. A flow cytometry analysis of blood samples from 44 healthy volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of NK-cells increased in females. The proportion of B-cells decreased in both sexes with age. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly, ANXA1 and CD36 showed a consistent increase with aging in all monocytes, specifically in intermediate (CD36) and intermediate and non-classical (ANXA1) subtypes. Other genes (IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91) were differentially changed in monocyte subtypes with increasing age. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction

Author

Safi, Fatemeh, primary, Dhapola, Parashar, additional, Warsi, Sarah, additional, Sommarin, Mikael, additional, Erlandsson, Eva, additional, Ungerbäck, Jonas, additional, Warfvinge, Rebecca, additional, Sitnicka, Ewa, additional, Bryder, David, additional, Böiers, Charlotta, additional, Thakur, Ram Krishna, additional, and Karlsson, Göran, additional

Published
2023
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10. LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis

Author

Peltzer, Nieves, Darding, Maurice, Montinaro, Antonella, Draber, Peter, Draberova, Helena, Kupka, Sebastian, Rieser, Eva, Fisher, Amanda, Hutchinson, Ciaran, Taraborrelli, Lucia, Hartwig, Torsten, Lafont, Elodie, Haas, Tobias L., Shimizu, Yutaka, Böiers, Charlotta, Sarr, Aida, Rickard, James, Alvarez-Diaz, Silvia, Ashworth, Michael T., Beal, Allison, Enver, Tariq, Bertin, John, Kaiser, William, Strasser, Andreas, Silke, John, Bouillet, Philippe, and Walczak, Henning

Published
2018
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14. Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells

Author

Böiers, Charlotta, Carrelha, Joana, Lutteropp, Michael, Luc, Sidinh, Green, Joanna C.A., Azzoni, Emanuele, Woll, Petter S., Mead, Adam J., Hultquist, Anne, Swiers, Gemma, Perdiguero, Elisa Gomez, Macaulay, Iain C., Melchiori, Luca, Luis, Tiago C., Kharazi, Shabnam, Bouriez-Jones, Tiphaine, Deng, Qiaolin, Pontén, Annica, Atkinson, Deborah, Jensen, Christina T., Sitnicka, Ewa, Geissmann, Frederic, Godin, Isabelle, Sandberg, Rickard, de Bruijn, Marella F.T.R., and Jacobsen, Sten Eirik W.

Published
2013
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26. Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy

Author

Sommarin, Mikael N.E., primary, Dhapola, Parashar, additional, Safi, Fatemeh, additional, Warfvinge, Rebecca, additional, Ulfsson, Linda Geironson, additional, Erlandsson, Eva, additional, Konturek-Ciesla, Anna, additional, Thakur, Ram Krishna, additional, Böiers, Charlotta, additional, Bryder, David, additional, and Karlsson, Göran, additional

Published
2021
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28. Generation and Trapping of a Mesoderm Biased State of Human Pluripotency

Author

Stavish, Dylan, primary, Böiers, Charlotta, additional, Price, Christopher, additional, Frith, Thomas J R, additional, Halliwell, Jason, additional, Barbaric, Ivana, additional, Brown, John, additional, Carr, Jonathon, additional, James, Chela, additional, Andrews, Peter W, additional, and Enver, Tariq, additional

Published
2019
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31. LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis

Author

Peltzer, Nieve, Darding, Maurice, Montinaro, Antonella, Draber, Peter, Draberova, Helena, Kupka, Sebastian, Rieser, Eva, Fisher, Amanda, Hutchinson, Ciaran, Taraborrelli, Lucia, Hartwig, Torsten, Lafont, Elodie, Haas, Tobias Longin, Shimizu, Yutaka, Böiers, Charlotta, Sarr, Aida, Rickard, Jame, Alvarez-Diaz, Silvia, Ashworth, Michael T., Beal, Allison, Enver, Tariq, Bertin, John, Kaiser, William, Strasser, Andrea, Silke, John, Bouillet, Philippe, Walczak, Henning, Haas, Tobias L. (ORCID:0000-0003-2336-0263), Peltzer, Nieve, Darding, Maurice, Montinaro, Antonella, Draber, Peter, Draberova, Helena, Kupka, Sebastian, Rieser, Eva, Fisher, Amanda, Hutchinson, Ciaran, Taraborrelli, Lucia, Hartwig, Torsten, Lafont, Elodie, Haas, Tobias Longin, Shimizu, Yutaka, Böiers, Charlotta, Sarr, Aida, Rickard, Jame, Alvarez-Diaz, Silvia, Ashworth, Michael T., Beal, Allison, Enver, Tariq, Bertin, John, Kaiser, William, Strasser, Andrea, Silke, John, Bouillet, Philippe, Walczak, Henning, and Haas, Tobias L. (ORCID:0000-0003-2336-0263)

Abstract

The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR11. Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8. In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11. Here we show, by creating HOIL-1-deficient mice, that HOIL-1 is as essential for LUBAC function as HOIP, albeit for different reasons: whereas HOIP is the catalytically active component of LUBAC, HOIL-1 is required for LUBAC assembly, stability and optimal retention in the TNFR1 signalling complex, thereby preventing aberrant cell death. Both HOIL-1 and HOIP prevent embryonic lethality at mid-gestation by interfering with aberrant TNFR1-mediated endothelial cell death, which only partially depends on RIPK1 kinase activity. Co-deletion of caspase-8 with RIPK3 or MLKL prevents cell death in Hoil-1-/-(also known as Rbck1-/-) embryos, yet only the combined loss of caspase-8 with MLKL results in viable HOIL-1-deficient mice. Notably, triple-knockout Ripk3-/-Casp8-/-Hoil-1-/-embryos die at late gestation owing to haematopoietic defects that are rescued by co-deletion of RIPK1 but not MLKL. Collectively, these results demonstrate that both HOIP and HOIL-1 are essential LUBAC components and are required for embryogenesis by preventing aberrant cell death. Furthermore, they reveal that when LUBAC and caspase-8 are absent, RIPK3 prevents RIPK1 from inducing embryonic lethality by causing defects in fetal haematopoiesis.

Published
2018

32. A human ips model implicates embryonic B-myeloid fate restriction as a developmental susceptibility to ETV6-RUNX1

Author

Böiers, Charlotta, primary, Richardson, Simon, additional, Zriwil, Alya, additional, Laycock, Emma, additional, Turati, Virginia, additional, Brown, John, additional, Wray, Jason, additional, Wang, Dapeng, additional, James, Chela, additional, Herrero, Javier, additional, Sitnicka, Ewa, additional, Karlsson, Stefan, additional, Smith, Andrew, additional, Jacobsen, Sten Erik, additional, and Enver, Tariq, additional

Published
2017
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34. Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors

Author

Luis, Tiago C, primary, Luc, Sidinh, additional, Mizukami, Takuo, additional, Boukarabila, Hanane, additional, Thongjuea, Supat, additional, Woll, Petter S, additional, Azzoni, Emanuele, additional, Giustacchini, Alice, additional, Lutteropp, Michael, additional, Bouriez-Jones, Tiphaine, additional, Vaidya, Harsh, additional, Mead, Adam J, additional, Atkinson, Deborah, additional, Böiers, Charlotta, additional, Carrelha, Joana, additional, Macaulay, Iain C, additional, Patient, Roger, additional, Geissmann, Frederic, additional, Nerlov, Claus, additional, Sandberg, Rickard, additional, de Bruijn, Marella F T R, additional, Blackburn, C Clare, additional, Godin, Isabelle, additional, and Jacobsen, Sten Eirik W, additional

Published
2016
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36. Embryonic thymopoiesis is initiated by an immune-restricted lympho-myeloid progenitor independently of notch signaling

Author

Luis, Tiago Cunha, primary, Luc, Sidinh, additional, Mizukami, Takuo, additional, Boukarabila, Hanane, additional, Thongjuea, Supat, additional, Woll, Petter, additional, Azzoni, Emanuele, additional, Lutteropp, Michael, additional, Bouriez-Jones, Tiphaine, additional, Vaidya, Harsh, additional, Mead, Adam, additional, Atkinson, Deborah, additional, Böiers, Charlotta, additional, Carrelha, Joana, additional, Macaulay, Iain, additional, Patient, Roger, additional, Nerlov, Claus, additional, Sandberg, Rickard, additional, de Bruijn, Marella, additional, Blackburn, C. Clare, additional, Godin, Isabelle, additional, and Jacobsen, Sten Eirik, additional

Published
2016
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38. Direct role of FLT3 in regulation of early lymphoid progenitors.

Author

Zriwil, Alya, Böiers, Charlotta, Kristiansen, Trine A., Wittmann, Lilian, Yuan, Joan, Nerlov, Claus, Sitnicka, Ewa, and Jacobsen, Sten E. W.

Subjects
*HEMATOPOIESIS, *PROGENITOR cells, *LEUKEMIA, *B cells, *T cells
Abstract

Summary: Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid‐primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock‐out (Flt3fl/fl) mouse model to address the direct role of FLT3 in regulation of lymphoid‐restricted progenitors, subsequent to turning on Rag1 expression, as well as potentially ontogeny‐specific roles in B and T lymphopoiesis. Our studies establish a prominent and direct role of FLT3, independently of the established role of FLT3 in regulation of LMPPs and CLPs, in regulation of fetal as well as adult early B cell progenitors, and the early thymic progenitors (ETPs) in adult mice but not in the fetus. Our findings highlight the potential benefit of targeting poor prognosis acute B‐cell progenitor leukaemia and ETP leukaemia with recurrent FLT3 mutations using clinical FLT3 inhibitors. [ABSTRACT FROM AUTHOR]

Published
2018
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41. Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells

Author

Böiers, C, Carrelha, J, Lutteropp, M, Luc, S, Green, J, Azzoni, E, Woll, P, Mead, A, Hultquist, A, Swiers, G, Perdiguero, E, Macaulay, I, Melchiori, L, Luis, T, Kharazi, S, Bouriez-Jones, T, Deng, Q, Pontén, A, Atkinson, D, Jensen, C, Sitnicka, E, Geissmann, F, Godin, I, Sandberg, R, de Bruijn, M, Jacobsen, S, Böiers, Charlotta, Carrelha, Joana, Lutteropp, Michael, Luc, Sidinh, Green, Joanna C A, Azzoni, Emanuele, Woll, Petter S, Mead, Adam J, Hultquist, Anne, Swiers, Gemma, Perdiguero, Elisa Gomez, Macaulay, Iain C, Melchiori, Luca, Luis, Tiago C, Kharazi, Shabnam, Bouriez-Jones, Tiphaine, Deng, Qiaolin, Pontén, Annica, Atkinson, Deborah, Jensen, Christina T, Sitnicka, Ewa, Geissmann, Frederic, Godin, Isabelle, Sandberg, Rickard, de Bruijn, Marella F T R, Jacobsen, Sten Eirik W, Böiers, C, Carrelha, J, Lutteropp, M, Luc, S, Green, J, Azzoni, E, Woll, P, Mead, A, Hultquist, A, Swiers, G, Perdiguero, E, Macaulay, I, Melchiori, L, Luis, T, Kharazi, S, Bouriez-Jones, T, Deng, Q, Pontén, A, Atkinson, D, Jensen, C, Sitnicka, E, Geissmann, F, Godin, I, Sandberg, R, de Bruijn, M, Jacobsen, S, Böiers, Charlotta, Carrelha, Joana, Lutteropp, Michael, Luc, Sidinh, Green, Joanna C A, Azzoni, Emanuele, Woll, Petter S, Mead, Adam J, Hultquist, Anne, Swiers, Gemma, Perdiguero, Elisa Gomez, Macaulay, Iain C, Melchiori, Luca, Luis, Tiago C, Kharazi, Shabnam, Bouriez-Jones, Tiphaine, Deng, Qiaolin, Pontén, Annica, Atkinson, Deborah, Jensen, Christina T, Sitnicka, Ewa, Geissmann, Frederic, Godin, Isabelle, Sandberg, Rickard, de Bruijn, Marella F T R, and Jacobsen, Sten Eirik W

Abstract

In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important lineage-commitment step in mammalian hematopoiesis

Published
2013

42. Establishment of lympho-myeloid restricted progenitors prior to the emergence of definitive hematopoietic stem cells

Author

Böiers, Charlotta, primary, Lutteropp, Michael, additional, Luc, Sidinh, additional, Woll, Petter, additional, Mead, Adam, additional, Hultquist, Anne, additional, Carrelha, Joana, additional, Macaulay, Iain, additional, Swiers, Gemma, additional, Melchiori, Luca, additional, Luis, Tiago, additional, Kharazi, Shabnam, additional, Bouriez-Jones, Tiphaine, additional, Deng, Qiaolin, additional, Pontén, Annica, additional, Jensen, Christina, additional, Sitnicka, Ewa, additional, Sandberg, Rickard, additional, de Bruijn, Marella, additional, and Jacobsen, Sten Eirik, additional

Published
2013
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45. In vitroclonal multilineage differentiation of distinct murine hematopoietic progenitor populations

Author

Safi, Fatemeh, Dhapola, Parashar, Erlandsson, Eva, Ulfsson, Linda Geironson, Calderón, Ariana S., Böiers, Charlotta, and Karlsson, Göran

Abstract

Here we describe an in vitroco-culture system that can differentiate hematopoietic progenitor populations to all major hematopoietic lineages at clonal level. We present both a sensitive single-cell switch-culture system as well as a less laborious alternative barcoding protocol more convenient for larger cell numbers. Importantly, generation of all lineages from single long-term hematopoietic stem cells are described, following 21 days of culture. This protocol represents an efficient tool for validation experiments for single-cell genomics data.

Published
2022
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46. In vitrodifferentiation of human pluripotent stem cells into the B lineage using OP9-MS5 co-culture

Author

Richardson, Simon E., Ghazanfari, Roshanak, Chhetri, Jyoti, Enver, Tariq, and Böiers, Charlotta

Abstract

In vitrodifferentiation of human pluripotent stem cells (hPSCs) offers a genetically tractable system to examine the physiology and pathology of human tissue development and differentiation. We have used this approach to model the earliest stages of human B lineage development and characterize potential target cells for the in uteroinitiation of childhood B acute lymphoblastic leukemia. Herein, we detail critical aspects of the protocol including reagent validation, controls and examples of surface markers used for analysis and cell sorting.

Published
2021
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