文章的通讯作者是中科院上海生命科学研究院营养所周斌研究员,以及哈佛大学医学院波士顿儿童医院华人科学家William Pu,其中周斌研究员早年毕业于浙江大学,主要研究方向是关键转录因子在心脏发育中的作用机制, 探索和心血管疾病相关的分子机理,以及心肌细胞再生。
心外膜是位于心脏表面的一层间皮细胞组成的膜,在心脏发育过程中起着重要的作用。缺少心外膜的心脏是不能正常发育的,缺少心外膜的小鼠死于胚胎早期。虽然心外膜在心脏发育过程中有着重要的作用,但在成体心脏受损修复过程中,心外膜如何发挥其重要功能还不清楚。
在这篇文章中,周斌研究组和William Pu研究组合作,利用转基因小鼠模型发现:心外膜细胞在心脏受损后发生上皮间质转换(EMT),形成间充质样细胞,通过分泌大量促血管新生因子,促进心脏冠脉内皮细胞增值,从而改善心梗后心脏功能的恢复。
哈佛大学William Pu研究组长年从事心脏疾病的研究,他们曾在Nature杂志上发表文章,发现了一组可培植心肌细胞的干细胞。研究人员认为当病人心脏出现问题时,便会失去驱动心跳的心肌细胞。唯一的补救方法就是制造更多这类细胞。
据悉,研究人员是在偶然的情况下发现新干细胞的。他们当时正在研究心外膜的另一组基因,所以要在活老鼠的胚胎上,用红色荧光蛋白复合体标签特定的细胞。出乎意料之外,他们竟然目睹心外膜细胞转化成心肌细胞。William Pu的研究成果显示,用基因编号为“Wt1”的干细胞能制造出心肌细胞、滑肌细胞及内皮细胞。
原文摘要:
Adult mouse epicardium modulates myocardial injury by secreting paracrine factors
The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection.
来源:生物通