Spatiotemporal Analysis Reveals Overlap of Key Proepicardial Markers in the Developing Murine Heart

• Published in: Stem cell reports Vol. 14; no. 5; pp. 770 - 787
• Main Authors: Lupu, Irina-Elena, Redpath, Andia N., Smart, Nicola
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.05.2020; Elsevier
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Lineage; EPDCs; epicardium; Fibroblasts - cytology; Fibroblasts - metabolism; heterogeneity; Mice; Mice, Inbred C57BL; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - metabolism; Muscle Cells - cytology; Muscle Cells - metabolism; Pericardium - cytology; Pericardium - embryology; Pericardium - metabolism; Pericytes - cytology; Pericytes - metabolism; proepicardium; Scx; Sema3d; Semaphorins - genetics; Semaphorins - metabolism; sub-compartment; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Tbx18; Tcf21; Wt1; WT1 Proteins - genetics; WT1 Proteins - metabolism; proepicardium; Sema3d; Wt1; EPDCs; Tcf21; epicardium; Scx; sub-compartment; heterogeneity; Tbx18
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2020.04.002

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. [Display omitted] •PEO and epicardial cells co-express Wt1, Sema3d, Tbx18, Scx, and Tcf21•Markers are not confined to (pro)epicardium and cannot individually define the lineage•Distinctive marker changes accompany epithelial-mesenchymal transition•Tcf21 is upregulated in epicardium-derived progenitors, other markers are downregulated Lupu, Redpath, and Smart systematically profile expression of canonical markers Wt1, Sema3d, Tbx18, Scx, and Tcf21 throughout murine cardiac development. They demonstrate overlapping expression in all proepicardial organ (PEO) and epicardial cells and describe how this marker signature changes upon epithelial-mesenchymal transition. Their findings refute the existence of discrete PEO sub-compartments with pre-determined fates.