中国科学院黄仕强课题组发现Lin28a维持成体肌肉干细胞(MuSCs)亚群处于胚胎样状态。2023年5月15日，国际知名学术期刊《细胞研究》发表了这一成果。

他们发现Lin28a在胚胎肢体芽肌祖细胞中表达，并且Lin28a+Pax7 -骨骼肌的一个罕见的储备亚群可以通过补充Pax7+ MuSC池来驱动肌肉再生，从而在成年阶段对损伤做出反应。与成人Pax7+ MuSCs相比，移植后Lin28a+ MuSCs在体外和体内表现出增强的成肌能力。成体Lin28a+ MuSCs的表观基因组与胚胎肌祖细胞相似。

此外，RNA测序显示，与成人Pax7+ MuSCs相比，Lin28a+ MuSCs共表达了更高水平的某些胚胎肢体芽转录因子、端粒酶组分和p53抑制剂Mdm4，以及更低水平的肌源分化标志物，从而增强了自我更新和应激反应特征。功能上，条件消融和诱导成年小鼠的Lin28a+ MuSCs表明，这些细胞对于有效的肌肉再生是必要和充分的。总之，他们的发现将胚胎因子Lin28a与成体干细胞自我更新和幼体再生联系起来。

研究人员表示，在稳态和损伤后，MuSC激活介导肌肉再生。然而，MuSC自我更新和再生的异质性能力仍不清楚。

附：英文原文

Title: Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state

Author: Wang, Peng, Liu, Xupeng, Yao, Ziyue, Chen, Yu, Luo, Lanfang, Liang, Kun, Tan, Jun-Hao Elwin, Chua, Min-Wen Jason, Chua, Yan-Jiang Benjamin, Ma, Shilin, Zhang, Liping, Ma, Wenwu, Liu, Shuqing, Cao, Wenhua, Guo, Luyao, Guang, Lu, Wang, Yuefan, Zhao, He, Ai, Na, Li, Yun, Li, Chunwei, Wang, Ruiqi Rachel, Teh, Bin Tean, Jiang, Lan, Yu, Kang, Shyh-Chang, Ng

Issue&Volume: 2023-05-15

Abstract: During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7– skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

DOI: 10.1038/s41422-023-00818-y

Source: https://www.nature.com/articles/s41422-023-00818-y