Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis.
emergency myelopoiesis
hematopoietic stem
mouse
myelopoiesis
polycomb repressive complex 1.1
progenitor cell
regenerative medicine
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
02 Jun 2023
02 Jun 2023
Historique:
received:
26
08
2022
accepted:
01
06
2023
medline:
26
6
2023
pubmed:
2
6
2023
entrez:
2
6
2023
Statut:
epublish
Résumé
Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPα-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.
Identifiants
pubmed: 37266576
doi: 10.7554/eLife.83004
pii: 83004
pmc: PMC10287155
doi:
pii:
Substances chimiques
Polycomb Repressive Complex 1
EC 2.3.2.27
Histones
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 19H05653
Organisme : Japan Society for the Promotion of Science
ID : 20K08728
Organisme : Japan Society for the Promotion of Science
ID : 19H05746
Organisme : Japan Agency for Medical Research and Development
ID : 21zf0127003h0001
Organisme : Japan Agency for Medical Research and Development
ID : JP223fa627001
Informations de copyright
© 2023, Nakajima-Takagi et al.
Déclaration de conflit d'intérêts
YN, MO, JT, SK, NI, SU, MY, SA, KA, YI, DS, AS, FA, KY, YF, HK, TI, AI No competing interests declared
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