Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX-75390, USA.
Development. 2012 Jun;139(12):2139-49. doi: 10.1242/dev.079970. Epub 2012 May 9.
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.
基本螺旋-环-螺旋 (bHLH) 转录因子家族在发育过程中协调多个细胞谱系中的细胞命运特化、决定和分化。在这里，我们描述了 bHLH 转录因子 Tcf21（心脏外胚层蛋白/ Pod1/ 帽蛋白）在心脏成纤维细胞谱系特化中的作用。在发育中的心脏中，心外膜构成了形成两个细胞谱系的祖细胞的主要来源：冠状动脉平滑肌细胞 (cVSMCs) 和心脏成纤维细胞。目前，关于这些谱系的特化是在心外膜形成的早期发生，还是在细胞进入心肌后发生，存在争议。使用从 Tcf21 基因座表达的他莫昔芬诱导型 Cre 进行的谱系追踪表明，在心脏外胚层上皮-间充质转化 (EMT) 开始之前，大多数表达 Tcf21 的心脏外膜细胞就已经决定了心脏成纤维细胞谱系。此外，Tcf21 缺失心脏未能形成心脏成纤维细胞，并且对缺失细胞的谱系追踪显示它们无法进行 EMT。这是第一个报道心脏成纤维细胞发育所必需的转录因子的报告。我们证明了 Tcf21 在多能性心脏外胚层祖细胞中的独特作用，在 EMT 过程之前，该过程对于心脏成纤维细胞的发育至关重要。
