期刊
CELL STEM CELL
卷 28, 期 7, 页码 1323-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2021.04.008
关键词
-
资金
- Glenn Foundation for Aging Research
- NIH [T32 AG000266, K99/R00 AG053438, P01 AG036695, TR01 AG047820, AG023806]
- Department of Veterans Affairs
The study revealed a molecular fate switch involving miR-206 and Runx1 that controls FAP differentiation to adipocytes. Lack of miR-206 results in increased adipogenesis in FAPs. miR-206 represses Runx1 translation, limiting intramuscular fatty infiltration.
Intramuscular fatty deposits, which are seen in muscular dystrophies and with aging, negatively affect muscle function. The cells of origin of adipocytes constituting these fatty deposits are mesenchymal stromal cells, fibroadipogenic progenitors (FAPs). We uncover a molecular fate switch, involving miR-206 and the transcription factor Runx1, that controls FAP differentiation to adipocytes. Mice deficient in miR-206 exhibit increased adipogenesis following muscle injury. Adipogenic differentiation of FAPs is abrogated by miR-206 mimics. Using a labeled microRNA (miRNA) pull-down and sequencing (LAMP-seq), we identified Runx1 as a miR-206 target, with miR-206 repressing Runx1 translation. In the absence of miR-206 in FAPs, Runx1 occupancy near transcriptional start sites of adipogenic genes and expression of these genes increase. We demonstrate that miR-206 mimicry in vivo limits intramuscular fatty infiltration. Our results provide insight into the underlying molecular mechanisms of FAP fate determination and formation of harmful fatty deposits in skeletal muscle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据