加拿大英属哥伦比亚大学T. Michael Underhill研究组发现，Hic1定义了在骨骼肌再生过程中具有不同功能和命运的静止间质祖亚群。2019年12月5日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

研究人员发现Hic1（Hypermethylated in cancer 1）是骨骼肌间充质祖细胞（MP）的标记，并进一步表明Hic1缺失导致MP增生。骨骼肌中Hic1⁺MP的单细胞RNA-seq和ATAC-seq分析显示了多个亚群，研究人员进一步发现它们具有独特的功能和谱系潜力。Hic1⁺MP通过提供阶段特异性的免疫调节以及营养和机械支持来协调骨骼肌再生的多个方面。在肌肉再生过程中，Hic1⁺衍生物直接参与多个间充质区室，包括肌腱接头内的Col22a1表达细胞。总的来说，这些发现表明，HIC1调节MP的静止并确立MP亚群在肌肉再生中具有短暂和持久作用。

据介绍，许多成人组织都包含常驻干细胞，例如骨骼肌内的Pax7+卫星细胞，这些干细胞在损伤后会再生实质成分。组织驻留MP也参与再生，尽管在此过程中它们的功能和命运尚不清楚。

附：英文原文

Title: Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration

Author: R. Wilder Scott, Martin Arostegui, Ronen Schweitzer, Fabio M.V. Rossi, T. Michael Underhill

Issue&Volume: 2019/12/05

Abstract: Many adult tissues contain resident stem cells, such as the Pax7+ satellite cells within skeletal muscle, that regenerate parenchymal elements following damage. Tissue-resident mesenchymal progenitors (MPs) also participate in regeneration, although their function and fate in this process are unclear. Here, we identify Hypermethylated in cancer 1 (Hic1) as a marker of MPs in skeletal muscle and further show that Hic1 deletion leads to MP hyperplasia. Single-cell RNA-seq and ATAC-seq analysis of Hic1+ MPs in skeletal muscle shows multiple subpopulations, which we further show have distinct functions and lineage potential. Hic1+ MPs orchestrate multiple aspects of skeletal muscle regeneration by providing stage-specific immunomodulation and trophic and mechanical support. During muscle regeneration, Hic1+ derivatives directly contribute to several mesenchymal compartments including Col22a1-expressing cells within the myotendinous junction. Collectively, these findings demonstrate that HIC1 regulates MP quiescence and identifies MP subpopulations with transient and enduring roles in muscle regeneration.

DOI: 10.1016/j.stem.2019.11.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30459-X