Prrx1标记成年小鼠骨骼、白色脂肪组织和真皮中的干细胞。

Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice.

作者信息

Liu Huijuan, Li Ping, Zhang Shaoyang, Xiang Jinnan, Yang Ruichen, Liu Jiajia, Shafiquzzaman Md, Biswas Soma, Wei Zhanying, Zhang Zhenlin, Zhou Xin, Yin Feng, Xie Yangli, Goff Stephen P, Chen Lin, Li Baojie

机构信息

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

出版信息

Nat Genet. 2022 Dec;54(12):1946-1958. doi: 10.1038/s41588-022-01227-4. Epub 2022 Dec 1.

DOI:10.1038/s41588-022-01227-4

PMID:36456880

Abstract

Specialized connective tissues, including bone and adipose tissues, control various physiological activities, including mineral and energy homeostasis. However, the identity of stem cells maintaining these tissues throughout adulthood remains elusive. By conducting genetic lineage tracing and cell depletion experiments in newly generated knock-in Cre/CreER lines, we show here that rare Prrx1-expressing cells act as stem cells for bone, white adipose tissue and dermis in adult mice, which are indispensable for the homeostasis and repair of these tissues. Single-cell profiling reveals the cycling and multipotent nature of Prrx1-expressing cells and the stemness of these cells is further validated by transplantation assays. Moreover, we identify the cell surface markers for Prrx1-expressing stem cells and show that the activities of these stem cells are regulated by Wnt signaling. These findings expand our knowledge of connective tissue homeostasis/regeneration and may help improve stem-cell-based therapies.

摘要

包括骨骼和脂肪组织在内的特殊结缔组织控制着各种生理活动，包括矿物质和能量稳态。然而，在成年期维持这些组织的干细胞身份仍然难以捉摸。通过在新生成的敲入型Cre/CreER品系中进行遗传谱系追踪和细胞耗竭实验，我们在此表明，成年小鼠中罕见的表达Prrx1的细胞充当骨骼、白色脂肪组织和真皮的干细胞，这对于这些组织的稳态和修复不可或缺。单细胞分析揭示了表达Prrx1的细胞的增殖和多能性质，并且这些细胞的干性通过移植实验得到进一步验证。此外，我们确定了表达Prrx1的干细胞的细胞表面标志物，并表明这些干细胞的活性受Wnt信号通路调节。这些发现扩展了我们对结缔组织稳态/再生的认识，并可能有助于改善基于干细胞的治疗方法。