Helios represses megakaryocyte priming in hematopoietic stem and progenitor cells.
Animals
Cell Differentiation
DNA-Binding Proteins
/ genetics
Female
Gene Expression Profiling
Gene Expression Regulation
Hematopoietic Stem Cells
/ cytology
Lymphocytes
/ cytology
Male
Megakaryocytes
/ cytology
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
T-Lymphocytes
/ cytology
Transcription Factors
/ genetics
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 10 2021
04 10 2021
Historique:
received:
30
10
2020
revised:
28
05
2021
accepted:
27
07
2021
entrez:
30
8
2021
pubmed:
31
8
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34459852
pii: 212608
doi: 10.1084/jem.20202317
pmc: PMC8406645
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Transcription Factors
0
Zfpn1a2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Marie Curie
ID : 813091
Pays : United Kingdom
Informations de copyright
© 2021 Cova et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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