Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

Yu Liu, Li Chen, Andrea Diaz Diaz, Ashley Benham, Xueping Xu, Cori S. Wijaya, Faisal Fa'Ak, Weijia Luo, Benjamin Soibam, Alon Azares, Wei Yu, Qiongying Lyu, M. David Stewart, Preethi Gunaratne, Austin Cooney, Bradley K. McConnell, Robert J. Schwartz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Mesp1 directs multipotential cardiovascular cell fates, even though it's transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1's transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1 Cre/+; Rosa26 EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells.

Original languageEnglish
Article number31457
JournalScientific reports
Volume6
DOIs
StatePublished - Aug 19 2016

Fingerprint

Dive into the research topics of 'Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts'. Together they form a unique fingerprint.

Cite this