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Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis
Yaeko Nakajima-Takagi1, Motohiko Oshima1, Junichiro Takano2
1Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Elife
|June 2, 2023
Summary
Polycomb repressive complex 1.1 (PRC1.1) balances blood cell production. Its transient inhibition is crucial for emergency myelopoiesis, while its loss drives myeloid transformation.
Area of Science:
- Epigenetics
- Hematopoiesis
- Stem cell biology
Background:
- Canonical Polycomb repressive complex 1 (PRC1) is vital for hematopoietic stem and progenitor cell (HSPC) maintenance.
- The role of non-canonical PRC1, specifically PRC1.1, in hematopoiesis is not well understood.
- PRC1.1 comprises PCGF1, RING1B, KDM2B, and BCOR.
Purpose of the Study:
- To investigate the role of PRC1.1 in coordinating homeostatic and emergency hematopoiesis.
- To determine how PRC1.1 regulates myeloid differentiation and stem cell self-renewal.
- To elucidate the consequences of PRC1.1 dysregulation in myeloid transformation.
Main Methods:
- Mouse models with PRC1.1 insufficiency (PCGF1 or BCOR loss).
- Analysis of hematopoietic stem and progenitor cell populations.
- Epigenetic regulation studies involving C/EBPα, HOXA9, and β-catenin pathways.
Main Results:
- PRC1.1 insufficiency leads to myeloid-biased hematopoiesis and hematopoietic cell transformation in mice.
- PRC1.1 restricts precocious myeloid differentiation and maintains self-renewal networks during steady-state hematopoiesis.
- Transient inhibition of PRC1.1 is required for emergency myelopoiesis by facilitating granulocyte-macrophage progenitor (GMP) cluster formation.
- Constitutive PRC1.1 inactivation causes uncontrolled GMP expansion and myeloid transformation.
Conclusions:
- PRC1.1 acts as an epigenetic switch coordinating homeostatic and emergency hematopoiesis.
- PRC1.1 is a novel critical regulator of emergency myelopoiesis.
- Dysregulation of PRC1.1 leads to myeloid transformation, highlighting its role in preventing leukemia development.
Keywords:
emergency myelopoiesishematopoietic stemmousemyelopoiesispolycomb repressive complex 1.1progenitor cellregenerative medicinestem cellsMore Related Videos
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