Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

HJames J.H. Chong, Vashe Chandrakanthan, Munira Xaymardan, Naisana S. Asli, Joan Li, Ishtiaq Ahmed, Corey Heffernan, Mary K. Menon, et al.

Colony-forming units-fibroblast (CFU-Fs), analogous to those giving rise to bonemarrow(BM)mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult cardiac-residentCFU-Fs (cCFU-Fs) that occupy a perivascular, adventitial niche and show broad trans-germ layer potency in vitro and in vivo. CRE lineage tracing and embryo analysis demonstrated a proepicardial origin for cCFU-Fs. Furthermore, in BMtransplantation chimeras, we found no interchange between BM and cCFU-Fs after aging, myocardial infarction, or BM stem cell mobilization. BM and cardiac and aortic CFU-Fs had distinct CRE lineage signatures, indicating that they arise from different progenitor beds during development. These diverse origins for CFU-Fs suggest an underlying basis for differentiation biases seen in different CFU-F populations, and could also influence their capacity for participating in tissue repair.

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