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美国华盛顿大学Jennifer Davis研究小组发现，MBNL1驱动心脏伤口愈合中成纤维细胞和肌成纤维细胞之间的动态转换。2022年2月16日，《细胞—干细胞》杂志在线发表了这项成果。

由于MBNL1（muscleblind-like 1）的转录组成熟促进了分化的细胞状态，研究人员调查了MBNL1活性的调控是否能改变肌成纤维细胞的活性和纤维化的结果。在健康小鼠中，心脏成纤维细胞特异性地过度表达MBNL1，使成纤维细胞转录组过渡到肌成纤维细胞，并在损伤后促进了肌细胞重塑和瘢痕成熟。纤维母细胞和肌纤维母细胞特异性的MBNL1缺失都限制了疤痕的产生和稳定，这是因为肌纤维母细胞的活性可以忽略不计。

MBNL1缺失和损伤的结合导致静止的成纤维细胞扩增并具有心脏间质干细胞的特征，而转基因的MBNL1表达阻止了成纤维细胞的增殖，并促使该群体进入成熟的肌成纤维细胞状态。这些数据表明MBNL1是一个转录后的开关，在心脏伤口愈合期间控制成纤维细胞的状态可塑性。

据了解，动态的成纤维细胞到肌成纤维细胞的状态转换是心脏纤维化反应的基础。

附：英文原文

Title: MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing

Author: Darrian Bugg, Logan R.J. Bailey, Ross C. Bretherton, Kylie E. Beach, Isabella M. Reichardt, Kalen Z. Robeson, Anna C. Reese, Jagadambika Gunaje, Galina Flint, Cole A. DeForest, April Stempien-Otero, Jennifer Davis

Issue&Volume: 2022-02-16

Abstract: Dynamic fibroblast to myofibroblast state transitions underlie the heart’s fibroticresponse. Because transcriptome maturation by muscleblind-like 1 (MBNL1) promotesdifferentiated cell states, this study investigated whether tactical control of MBNL1activity could alter myofibroblast activity and fibrotic outcomes. In healthy mice,cardiac fibroblast-specific overexpression of MBNL1 transitioned the fibroblast transcriptometo that of a myofibroblast and after injury promoted myocyte remodeling and scar maturation.Both fibroblast- and myofibroblast-specific loss of MBNL1 limited scar productionand stabilization, which was ascribed to negligible myofibroblast activity. The combinationof MBNL1 deletion and injury caused quiescent fibroblasts to expand and adopt featuresof cardiac mesenchymal stem cells, whereas transgenic MBNL1 expression blocked fibroblastproliferation and drove the population into a mature myofibroblast state. These datasuggest MBNL1 is a post-transcriptional switch, controlling fibroblast state plasticityduring cardiac wound healing.

DOI: 10.1016/j.stem.2022.01.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00035-2

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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