Downregulation of LGR5 Expression Inhibits Cardiomyocyte Differentiation and Potentiates Endothelial Differentiation from Human Pluripotent Stem Cells

• Type of Material: Article
• Authors: Rajneesh Jha, Emory University; Monalisa Singh, Emory University; Qingling Wu, Emory University; Cinsley Gentillon, Emory University; Marcela K. Preininger, Emory University; Chunhui Xu, Emory University
• Language: English
• Date: 2017-08-08
• Publisher: Elsevier (Cell Press)
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.stemcr.2017.07.006
• Title of Journal or Parent Work: Stem Cell Reports
• ISSN: 2213-6711
• Volume: 9
• Issue: 2
• Start Page: 513
• End Page: 527
• Grant/Funding Information: This study was supported in part by grants GA-2014-126 from the Center for the Advancement of Science in Space, R21 HL123928 from the NIH, and 16GRNT30090002 from the American Heart Association.; Q.W. and M.K.P. were supported by the Center for Pediatric Nanomedicine at Emory/Georgia Tech.
• Keywords: GENE; Life Sciences & Biomedicine; WNT RECEPTORS; Cell Biology; COUPLED RECEPTOR GPR49; WNT/BETA-CATENIN; EFFICIENT DIFFERENTIATION; CARDIAC DIFFERENTIATION; MOUSE; PROTEIN; IN-VITRO; Cell & Tissue Engineering; Science & Technology; PROLIFERATION
• Research Categories: Health Sciences, General; Engineering, Biomedical

Abstract

Understanding molecules involved in differentiation of human pluripotent stem cells (hPSCs) into cardiomyocytes and endothelial cells is important in advancing hPSCs for cell therapy and drug testing. Here, we report that LGR5, a leucine-rich repeat-containing G-protein-coupled receptor, plays a critical role in hPSC differentiation into cardiomyocytes and endothelial cells. LGR5 expression was transiently upregulated during the early stage of cardiomyocyte differentiation, and knockdown of LGR5 resulted in reduced expression of cardiomyocyte-associated markers and poor cardiac differentiation. In contrast, knockdown of LGR5 promoted differentiation of endothelial-like cells with increased expression of endothelial cell markers and appropriate functional characteristics, including the ability to form tube-like structures and to take up acetylated low-density lipoproteins. Furthermore, knockdown of LGR5 significantly reduced the proliferation of differentiated cells and increased the nuclear translocation of β-catenin and expression of Wnt signaling-related genes. Therefore, regulation of LGR5 may facilitate efficient generation of cardiomyocytes or endothelial cells from hPSCs.