c-kit is required for cardiomyocyte terminal differentiation.

Content Provider	Semantic Scholar
Author	Li, Ming Qing Naqvi, N. Farzana Yahiro, Eiji Liu, Ke Powell, Pamela Cox Bradley, Wayne E. Martin, David I. K. Graham, Robert M. Dell'Italia, Louis J. Husain, A. M. Mahmood
Copyright Year	2008
Abstract	c-kit, the transmembrane tyrosine kinase receptor for stem cell factor, is required for melanocyte and mast cell development, hematopoiesis, and differentiation of spermatogonial stem cells. We show here that in the heart, c-kit is expressed not only by cardiac stem cells but also by cardiomyocytes, commencing immediately after birth and terminating a few days later, coincident with the onset of cardiomyocyte terminal differentiation. To examine the function of c-kit in cardiomyocyte terminal differentiation, we used compound heterozygous mice carrying the W (null) and W(v) (dominant negative) mutations of c-kit. In vivo, adult W/W(v) cardiomyocytes are phenotypically indistinguishable from their wild-type counterparts. After acute pressure overload adult W/W(v) cardiomyocytes reenter the cell cycle and proliferate, leading to left ventricular growth; furthermore in transgenic mice with cardiomyocyte-restricted overexpression of the dominant negative W(v) mutant, pressure overload causes cardiomyocytes to reenter the cell cycle. In contrast, in wild-type mice left ventricular growth after pressure overload results mainly from cardiomyocyte hypertrophy. Importantly, W/W(v) mice with pressure overload-induced cardiomyocyte hyperplasia had improved left ventricular function and survival. In W/W(v) mice, c-kit dysfunction also resulted in an approximately 14-fold decrease (P<0.01) in the number of c-kit(+)/GATA4(+) cardiac progenitors. These findings identify novel functions for c-kit: promotion of cardiac stem cell differentiation and regulation of cardiomyocyte terminal differentiation.
Starting Page	501
Ending Page	515
Page Count	15
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/102/6/677.full.pdf?download=true
PubMed reference number	18258857v1
Alternate Webpage(s)	https://doi.org/10.1161/CIRCRESAHA.107.161737
DOI	10.1161/circresaha.107.161737
Journal	Circulation research
Volume Number	102
Issue Number	6
Language	English
Access Restriction	Open
Subject Keyword	Cardiac Stem Cell Cell Cycle Cell Differentiation process Cell development Dominant-Negative Mutation Hematopoiesis Hypertrophy Left Ventricular Function Mast/Stem Cell Growth Factor Receptor Kit, human Myocytes, Cardiac Null Value Protein Tyrosine Kinase Stem Cell Differentiation Stem cells mast cell
Content Type	Text
Resource Type	Article