AI Article Synopsis
- PRC1 regulates stem cell fate through the modification of histone H2A and is essential for maintaining hematopoietic stem and progenitor cells (HSPCs), but the function of non-canonical PRC1 (specifically PRC1.1) in hematopoiesis is not well understood.
- Research shows that a lack of PRC1.1, due to loss of specific components like PCGF1 or BCOR, results in a bias towards myeloid cell development and can lead to cell transformation in mice.
- PRC1.1 acts as a critical regulator in maintaining a balance between normal and emergency hematopoiesis, controlling myeloid differentiation and affecting the formation of progenitor
Article 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/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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287155 | PMC |
| http://dx.doi.org/10.7554/eLife.83004 | DOI Listing |
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