title: Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts.
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.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors.forename: Andrea Diaz
authors.initials: AD
authors.lastname: Diaz
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Benham
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Xueping
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors.forename: Cori S
authors.initials: CS
authors.lastname: Wijaya
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors.forename: Faisal
authors.initials: F
authors.lastname: Fa'ak
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Weijia
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Computer Science and Engineering Technology, University of Houston-Downtown, Houston, 77002, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Soibam
authors.affiliation: Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030, USA.
authors.forename: Alon
authors.initials: A
authors.lastname: Azares
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Qiongying
authors.initials: Q
authors.lastname: Lyu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.|Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030, USA.
authors.forename: M David
authors.initials: MD
authors.lastname: Stewart
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Preethi
authors.initials: P
authors.lastname: Gunaratne
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Cooney
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: McConnell
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.|Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D006321:Heart / Q000000981:diagnostic imaging; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D060509:Wnt3A Protein; C101538:Mesp1 protein, mouse