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

作　　者：Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai 

机构地区：[1]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Taikang Center for Life and Medical Sciences,Wuhan University,Wuhan 430079,China [2]Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University,Xi’an 710004,China [3]Department of Implant Dentistry,College of Stomatology,Xi’an Jiaotong University,Xi’an 710004,China [4]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi Key Laboratory of Stomatology,Shaanxi International Joint Research Center for Oral Diseases,Center for Tissue Engineering,School of Stomatology,The Fourth Military Medical University,Xi’an 710032,China [5]State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China [6]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi Key Laboratory of Stomatology,Department of Oral and Maxillofacial Surgery,School of Stomatology,The Fourth Military Medical University,Xi’an 710032,China [7]Department of Hematology,Zhongnan Hospital,Wuhan University,Wuhan 430079,China [8]Frontier Science Center for Immunology and Metabolism,Medical Research Institute,Wuhan University,Wuhan 430079,China [9]Taikang Center for Life and Medical Sciences,Wuhan University,Wuhan 430079,China

出　　处：《Science Bulletin》2024年第13期2099-2113,共15页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2022YFA0103200);the National Natural Science Foundation of China(82325003,82230007,82200188,82270956 and 82171568);the National Defense Biotechnology Outstanding Young Talents Fund(01-SWKJYCJJ24);Shaanxi Province Innovation Capability Support Program Scientific and Technological Innovation Team(2023-CX-TD-69).

摘　　要：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.

关 键 词：Skeletal stem cells Bone development Epigenetics Ptip GLYCOLYSIS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]