Irx4 Marks a Multipotent, Ventricular-Specific Progenitor Cell. (13th September 2016)

• Record Type: Journal Article
• Authors: Nelson, Daryl O.; Lalit, Pratik A.; Biermann, Mitch; Markandeya, Yogananda S.; Capes, Deborah L.; Addesso, Luke; Patel, Gina; Han, Tianxiao; John, Manorama C.; Powers, Patricia A.; Downs, Karen M.; Kamp, Timothy J.; Lyons, Gary E.
• Is Part Of: Stem cells. Volume 34:Number 12(2016:Dec.)
• Page Start: 2875
• Page End: 2888
• Publication Date: 2016-09-13
• Subjects: Cardiac -- Developmental biology -- Differentiation -- Embryonic stem cells -- Stem cell transplantation -- Progenitor cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2486
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: While much progress has been made in the resolution of the cellular hierarchy underlying cardiogenesis, our understanding of chamber-specific myocardium differentiation remains incomplete. To better understand ventricular myocardium differentiation, we targeted the ventricle-specific gene, Irx4, in mouse embryonic stem cells to generate a reporter cell line. Using an antibiotic-selection approach, we purified Irx4 + cells in vitro from differentiating embryoid bodies. The isolated Irx4 + cells proved to be highly proliferative and presented Cxcr4, Pdgfr-alpha, Flk1, and Flt1 on the cell surface. Single Irx4 + ventricular progenitor cells (VPCs) exhibited cardiovascular potency, generating endothelial cells, smooth muscle cells, and ventricular myocytes in vitro. The ventricular specificity of the Irx4 + population was further demonstrated in vivo as VPCs injected into the cardiac crescent subsequently produced Mlc2v + myocytes that exclusively contributed to the nascent ventricle at E9.5. These findings support the existence of a newly identified ventricular myocardial progenitor. This is the first report of a multipotent cardiac progenitor that contributes progeny specific to the ventricular myocardium. Stem Cells 2016;34:2875–2888 Abstract : The Irx4 locus was targeted in mouse embryonic stem cells (mESCs) allowing antibiotic selection with hygromycin of Irx4 + ventricular progenitor cells (VPCs) during embryoid body differentiation. The Irx4 + VPCs were proliferative and multipotent differentiating in vivo to ventricular cardiomyocytes, endothelial cells and smooth muscle cells as well as differentiating when injected into the cardiac crescent of the developing mouse embryo into ventricular cardiomyocytes.