The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors
The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors
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DOI：
10.1242/dev.079970
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发表时间：
2012-06-15
期刊：
影响因子：
4.6
通讯作者：
Tallquist, Michelle D.
中科院分区：
文献类型：
--
作者：
Acharya, Asha;Baek, Seung Tae;Tallquist, Michelle D.
基本螺旋-环-螺旋（bHLH）转录因子家族在发育过程中协调多种细胞系的细胞命运规范、承诺和分化。在这里，我们描述了bHLH转录因子Tcf21 （epicardin/Pod1/capsulin）在心脏成纤维细胞谱系中的作用。在发育中的心脏中，心外膜是形成两种细胞系的祖细胞的主要来源：冠状动脉血管平滑肌细胞（cVSMCs）和心脏成纤维细胞。目前，关于这些谱系的分化是发生在心外膜形成的早期，还是发生在细胞进入心肌后，存在争议。使用从Tcf21位点表达的他莫昔芬诱导的Cre进行谱系追踪表明，大多数表达Tcf21的心外膜细胞在心外膜上皮细胞向间质细胞转化（EMT）开始之前，就已经进入了心脏成纤维细胞谱系。此外，Tcf21缺失的心脏不能形成心脏成纤维细胞，并且对这些缺失细胞的谱系追踪显示它们不能进行EMT。这是首次报道心脏成纤维细胞发育所必需的转录因子。我们证明了Tcf21在多能心外膜祖细胞中的独特作用，在EMT过程之前，这是心脏成纤维细胞发育所必需的。
The basic helix-loop-helix (bHLH) family of transcription factors orchestrates cell-fate specification, commitment and differentiation in multiple cell lineages during development. Here, we describe the role of a bHLH transcription factor, Tcf21 (epicardin/Pod1/capsulin), in specification of the cardiac fibroblast lineage. In the developing heart, the epicardium constitutes the primary source of progenitor cells that form two cell lineages: coronary vascular smooth muscle cells (cVSMCs) and cardiac fibroblasts. Currently, there is a debate regarding whether the specification of these lineages occurs early in the formation of the epicardium or later after the cells have entered the myocardium. Lineage tracing using a tamoxifen-inducible Cre expressed from the Tcf21 locus demonstrated that the majority of Tcf21-expressing epicardial cells are committed to the cardiac fibroblast lineage prior to initiation of epicardial epithelial-to-mesenchymal transition (EMT). Furthermore, Tcf21 null hearts fail to form cardiac fibroblasts, and lineage tracing of the null cells showed their inability to undergo EMT. This is the first report of a transcription factor essential for the development of cardiac fibroblasts. We demonstrate a unique role for Tcf21 in multipotent epicardial progenitors, prior to the process of EMT that is essential for cardiac fibroblast development.