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Helios represses megakaryocyte priming in hematopoietic stem and progenitor cells
- Source :
- Journal of Experimental Medicine, Journal of Experimental Medicine, 2021, 218 (10), pp.e20202317. ⟨10.1084/jem.20202317⟩, Journal of Experimental Medicine, Rockefeller University Press, 2021, 218 (10), ⟨10.1084/jem.20202317⟩
- Publication Year :
- 2021
- Publisher :
- Umeå universitet, Umeå centrum för molekylär medicin (UCMM), 2021.
-
Abstract
- International audience; Our understanding of cell fate decisions in hematopoietic stem cells is incomplete. Here, we show that the transcription factor Helios is highly expressed in murine hematopoietic stem and progenitor cells (HSPCs), where it is required to suppress the separation of the platelet/megakaryocyte lineage from the HSPC pool. Helios acts mainly in quiescent cells, where it directly represses the megakaryocyte gene expression program in cells as early as the stem cell stage. Helios binding promotes chromatin compaction, notably at the regulatory regions of platelet-specific genes recognized by the Gata2 and Runx1 transcriptional activators, implicated in megakaryocyte priming. Helios null HSPCs are biased toward the megakaryocyte lineage at the expense of the lymphoid and partially resemble cells of aging animals. We propose that Helios acts as a guardian of HSPC pluripotency by continuously repressing the megakaryocyte fate, which in turn allows downstream lymphoid priming to take place. These results highlight the importance of negative and positive priming events in lineage commitment.
- Subjects :
- Male
[SDV]Life Sciences [q-bio]
T-Lymphocytes
Immunology
Priming (immunology)
Mice, Transgenic
HeliOS
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Megakaryocyte
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
medicine
Immunology and Allergy
Animals
Lymphocytes
Hematologi
Progenitor cell
030304 developmental biology
Mice, Knockout
0303 health sciences
Gene Expression Profiling
GATA2
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Cell Differentiation
Hematology
Hematopoietic Stem Cells
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
Haematopoiesis
medicine.anatomical_structure
RUNX1
chemistry
Gene Expression Regulation
Female
Stem cell
Megakaryocytes
030215 immunology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine, Journal of Experimental Medicine, 2021, 218 (10), pp.e20202317. ⟨10.1084/jem.20202317⟩, Journal of Experimental Medicine, Rockefeller University Press, 2021, 218 (10), ⟨10.1084/jem.20202317⟩
- Accession number :
- edsair.doi.dedup.....fa67fa174402716bd69ba0708bdaf889