European Research Institute for Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), The Netherlands.
Sanquin Research, Landsteiner Laboratory, Sanquin Blood Supply, Amsterdam, The Netherlands.
FEBS Lett. 2024 Nov;598(22):2788-2806. doi: 10.1002/1873-3468.14839. Epub 2024 Mar 1.
Hematopoietic stem cell (HSC) fate decisions are dictated by epigenetic landscapes. The Polycomb Repressive Complex 1 (PRC1) represses genes that induce differentiation, thereby maintaining HSC self-renewal. Depending on which chromobox (CBX) protein (CBX2, CBX4, CBX6, CBX7, or CBX8) is part of the PRC1 complex, HSC fate decisions differ. Here, we review how this occurs. We describe how CBX proteins dictate age-related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non-epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non-epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells.
造血干细胞（HSC）的命运决定受表观遗传景观的支配。多梳抑制复合物 1（PRC1）抑制诱导分化的基因，从而维持 HSC 的自我更新。根据 PRC1 复合物中包含的哪个 chromobox（CBX）蛋白（CBX2、CBX4、CBX6、CBX7 或 CBX8），HSC 的命运决定会有所不同。在这里，我们回顾一下这种情况是如何发生的。我们描述了 CBX 蛋白如何决定与年龄相关的 HSC 变化，并通过经典的 PRC1 成员或替代相互作用（包括非表观遗传调控）刺激致癌性 HSC 命运决定。CBX2、CBX7 和 CBX8 增强白血病的进展。为了靶向、重编程和杀死白血病细胞，我们建议并描述了多种治疗策略来干扰致癌 CBX 蛋白的表观遗传功能。未来的研究应该阐明细胞质 CBX 蛋白的非表观遗传功能对正常、衰老和白血病血细胞的重要程度。
