Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis
- University of Tokyo, Japan
- RIKEN Center for Integrative Medical Sciences, Japan
- Chiba University, Japan
- Kyushu University, Japan
- Tokyo University of Science, Japan
Abstract
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/EBPa-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.
Data availability
RNA sequence, ChIP sequence and ATAC sequence data were deposited in the DDBJ (accession number DRA008518 and DRA013523).
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Non-canonical PRC1 orchestrates homeostatic and emergency hematopoiesis and restricts transformation by acting as a rheostat of myeloid differentiationDDBJ, DRR180690-DRR180705, DRR180730-DRR180735, DRR180742, DRR180743, DRR180746, DRR180747.
Article and author information
Author details
Masayuki Yamashita
Funding
Japan Society for the Promotion of Science (19H05653)
- Atsushi Iwama
Japan Society for the Promotion of Science (20K08728)
- Yaeko Nakajima-Takagi
Japan Society for the Promotion of Science (19H05746)
- Atsushi Iwama
Japan Agency for Medical Research and Development (21zf0127003h0001)
- Atsushi Iwama
Japan Agency for Medical Research and Development (JP223fa627001)
- Atsushi Iwama
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments using mice were performed in accordance with our institutional guidelines for the use of laboratory animals and approved by the Review Board for Animal Experiments of Chiba University (approval ID: 30-56) and the University of Tokyo (approval ID: PA18-03).
Copyright
© 2023, Nakajima-Takagi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis
eLife 12:e83004.
https://doi.org/10.7554/eLife.83004
