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Epigenetic regulator Ptip safeguards skeletal - EurekAlert
Stem cells keep a quiescent state for long-term maintenance and preserving potency which requires fine-tuning regulatory mechanisms. Jianfei Liang et al. 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). They found Ptip is required for maintaining the quiescence and potency of SSC, and loss of Ptip in type II collagen (Col2)+ progenitors results in abnormal activation and differentiation of SSC, impaired growth plate morphogenesis and long bone dysplasia. Mechanically, Ptip is further revealed to suppress glycolysis of SSC via downregulating Phosphoglycerate kinase 1 (Pgk1), which is based on repressing histone H3 lysine 27 acetylation (H3K27ac) modification at the promoter region. Notably, inhibition of glycolysis improves the function of SSC despite Ptip deficiency. These findings first establish an epigenetic framework defined by Ptip safeguarding skeletal stem cell quiescence and potency through metabolic control, which enlightens SSC-based treatments of bone developmental disorders.
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