武汉大学Yi Bai，Haojian Zhang和第四军医大学Liang Kong共同合作，近期取得重要工作进展。他们研究提出，Ptip在骨骼形成过程中能保护骨骼干细胞静止和效力的表观遗传学调控。相关研究成果2024年2月29日在线发表于《科学通报》杂志上。

据介绍，干细胞保持静息状态以长期维持和保存效力，这一过程需要对监管机制进行精密的调控。

研究人员确定了骨骼发生过程中骨骼干细胞（SSC）发育轨迹的表观遗传学概况，该发育过程由关键调节因子Ptip（也称为Paxip1，Pax与转录激活域蛋白-1的相互作用）控制。研究结果表明，Ptip是维持SSC静止和效力所必需的，II型胶原（Col2）⁺祖细胞中Ptip的缺失会导致SSC的异常激活和分化、生长板形态发生受损和长骨发育不良。

研究人员还发现，Ptip通过抑制启动子区的组蛋白H3赖氨酸27位乙酰化（H3K27ac）下调磷酸甘油酸激酶1（Pgk1）来抑制SSC的糖酵解。值得注意的是，尽管Ptip缺乏，但糖酵解的抑制改善了SSC的功能。

总之，研究人员提出，这是第一项建立基于Ptip的表观遗传学框架的研究，该框架通过代谢控制来保护骨骼干细胞的静止和效力，有望改善基于SSC的骨发育障碍治疗。

附：英文原文

Title: Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

Author: anonymous

Issue&Volume: 2024/02/29

Abstract: Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3 lysine 27 acetylation (H3K27ac) at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

DOI: 10.1016/j.scib.2024.02.036

Source: https://www.sciencedirect.com/science/article/pii/S2095927324001385