关键词: EPDCs Scx Sema3d Tbx18 Tcf21 Wt1 epicardium heterogeneity proepicardium sub-compartment

Mesh : Animals Basic Helix-Loop-Helix Transcription Factors / genetics metabolism Cell Lineage Fibroblasts / cytology metabolism Mice Mice, Inbred C57BL Mouse Embryonic Stem Cells / cytology metabolism Muscle Cells / cytology metabolism Pericardium / cytology embryology metabolism Pericytes / cytology metabolism Semaphorins / genetics metabolism T-Box Domain Proteins / genetics metabolism WT1 Proteins / genetics metabolism

来  源:   DOI:10.1016/j.stemcr.2020.04.002   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
The embryonic epicardium, originating from the proepicardial organ (PEO), provides a source of multipotent progenitors for cardiac lineages, including pericytes, fibroblasts, and vascular smooth muscle cells. Maximizing the regenerative capacity of the adult epicardium depends on recapitulating embryonic cell fates. The potential of the epicardium to contribute coronary endothelium is unclear, due to conflicting Cre-based lineage trace data. Controversy also surrounds when epicardial cell fate becomes restricted. Here, we systematically investigate expression of five widely used epicardial markers, Wt1, Tcf21, Tbx18, Sema3d, and Scx, over the course of development. We show overlap of markers in all PEO and epicardial cells until E13.5, and find no evidence for discrete proepicardial sub-compartments that might contribute coronary endothelium via the epicardial layer. Our findings clarify a number of prevailing discrepancies and support the notion that epicardium-derived cell fate, to form fibroblasts or mural cells, is specified after epithelial-mesenchymal transition, not pre-determined within the PEO.
摘要:
胚胎心外膜,起源于心外膜前器官(PEO),为心脏谱系提供了多能祖细胞的来源,包括周细胞,成纤维细胞,血管平滑肌细胞.成年心外膜的再生能力最大化取决于对胚胎细胞命运的概括。心外膜促进冠状动脉内皮的潜力尚不清楚,由于冲突的基于Cre的沿袭跟踪数据。当心外膜细胞命运受到限制时,争议也围绕着。这里,我们系统地研究了五种广泛使用的心外膜标志物的表达,WT1,Tcf21,Tbx18,Sema3d,和Scx,在发展过程中。我们显示了所有PEO和心外膜细胞中标记物的重叠,直到E13.5,并且没有发现离散的心外膜亚隔室可能通过心外膜层促进冠状动脉内皮的证据。我们的发现澄清了一些普遍存在的差异,并支持心外膜来源的细胞命运,形成成纤维细胞或壁细胞,在上皮-间质转化后指定,在PEO内不是预先确定的。
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