近日，美国加州大学旧金山分校Andrew S. Brack研究组发现储备肌干细胞亚群能够在压力下实现克隆扩增。相关论文于2019年6月发表在国际知名学术期刊《Cell Stem Cell》杂志上。

干细胞的异质性在功能上被认为与组织内稳态和修复相关。骨骼肌卫星细胞亚群的细胞身份、背景依赖性以及调控仍不清楚。

研究人员鉴定到一小群Pax7阳性的卫星细胞，这群细胞能够在体内被诱导型Mx1-Cre转基因所标记，并存在Pax3基因高表达，以及具有较低的活性氧水平。Mx1阳性的卫星细胞在移植实验中表现出很强的干细胞活性，但由于其丰度相对较低，对内源性肌肉修复的贡献微乎其微。相比之下，当处在选择性的放射压力条件下，Mx1阳性的卫星细胞出现剧烈克隆扩增，从而大量贡献于肌肉修复和微环境重塑，这与储备肌干细胞的特性一致。在储备肌干细胞中敲除Pax3基因会增加ROS含量，并降低其压力耐受和存活能力。因此，这些发现表明，Pax7阳性的卫星细胞池含有一类不同的放射耐受储备肌干细胞具有在严重压力条件下的克隆扩增能力。

附：英文原文

Title: Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress

Author: Annarita Scaramozza, Dongsu Park, Swapna Kollu, Isabel Beerman, Xuefeng Sun, Derrick J. Rossi, Charles P. Lin, David T. Scadden, Colin Crist, Andrew S. Brack

Issue&Volume: Jun 06, 2019 Volume 24Issue 6

Abstract: Stem cell heterogeneity is recognized as functionally relevant for tissue homeostasis and repair. The identity, context dependence, and regulation of skeletal muscle satellite cell (SC) subsets remains poorly understood. We identify a minor subset of Pax7 + SCs that is indelibly marked by an inducible Mx1-Cre transgene in vivo, is enriched for Pax3 expression, and has reduced ROS (reactive oxygen species) levels. Mx1 + SCs possess potent stem cell activity upon transplantation but minimally contribute to endogenous muscle repair, due to their relative low abundance. In contrast, a dramatic clonal expansion of Mx1 + SCs allows extensive contribution to muscle repair and niche repopulation upon selective pressure of radiation stress, consistent with reserve stem cell (RSC) properties. Loss of Pax3 in RSCs increased ROS content and diminished survival and stress tolerance. These observations demonstrate that the Pax7 + SC pool contains a discrete population of radiotolerant RSCs that undergo clonal expansion under severe stress.

DOI: https://doi.org/10.1016/j.stem.2019.03.020

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30119-5