Downregulation of LGR5 Expression Inhibits Cardiomyocyte Differentiation and Potentiates Endothelial Differentiation from Human Pluripotent Stem Cells.
Downregulation of LGR5 Expression Inhibits Cardiomyocyte Differentiation and Potentiates Endothelial Differentiation from Human Pluripotent Stem Cells.
复制标题
DOI：
10.1016/j.stemcr.2017.07.006
复制
发表时间：
2017-08-08
影响因子：
5.9
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Jha R;Singh M;Wu Q;Gentillon C;Preininger MK;Xu C
了解参与人类多能干细胞 (hPSC) 分化为心肌细胞和内皮细胞的分子对于推进 hPSC 用于细胞治疗和药物测试非常重要。在此，我们报道 LGR5 是一种富含亮氨酸重复序列的 G 蛋白偶联受体，在 hPSC 分化为心肌细胞和内皮细胞的过程中发挥着关键作用。 LGR5表达在心肌细胞分化早期短暂上调，敲低LGR5会导致心肌细胞相关标志物表达减少和心脏分化不良。相比之下，LGR5的敲除促进了内皮样细胞的分化，增加了内皮细胞标记物的表达和适当的功能特征，包括形成管状结构和摄取乙酰化低密度脂蛋白的能力。此外，LGR5的敲低显着减少了分化细胞的增殖，并增加了β-连环蛋白的核转位和Wnt信号相关基因的表达。因此，LGR5的调节可能有助于hPSC有效生成心肌细胞或内皮细胞。 LGR5 表达在心肌细胞分化的早期阶段上调 LGR5 的敲低抑制心肌细胞的分化 LGR5 的敲低增加内皮细胞的分化 LGR5 的敲低降低 Wnt 信号相关基因的表达 在这篇文章中，Xu 及其同事证明，LGR5（富含亮氨酸重复序列的 G 蛋白偶联受体 5）在人多能干细胞的心肌细胞和内皮分化中发挥着关键作用。 LGR5的表达在心肌细胞分化的早期阶段短暂上调，LGR5的敲除导致心肌细胞分化减少但内皮细胞分化增加。
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. LGR5 expression is upregulated in the early stage of cardiomyocyte differentiation Knockdown of LGR5 inhibits differentiation of cardiomyocytes Knockdown of LGR5 increases differentiation of endothelial cells Knockdown of LGR5 decreases the expression of Wnt signaling-related genes In this article, Xu and colleagues demonstrate that LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5) plays a critical role in cardiomyocytes and endothelial differentiation from human pluripotent stem cells. Expression of LGR5 is transiently upregulated during the early stage of cardiomyocyte differentiation, and knockdown of LGR5 results in reduced cardiomyocyte differentiation but increased endothelial differentiation.
登录
查看更多内容
体外人类内皮细胞的系列传播。
影响因子：
7.8
作者：
Maciag, T;Hoover, G A;Stemerman, M B;Weinstein, R
通讯作者：
Weinstein, R
影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
8.8
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
23.9
作者：
Gu, Wen;Gaeta, Xavier;Sahakyan, Anna;Chan, Alanna B.;Hong, Candice S.;Kim, Rachel;Braas, Daniel;Plath, Kathrin;Lowry, William E.;Christofk, Heather R.
通讯作者：
Christofk, Heather R.
影响因子：
5.9
作者：
Mazzotta, Silvia;Neves, Carlos;Bonner, Rory J.;Bernardo, Andreia S.;Docherty, Kevin;Hoppler, Stefan
通讯作者：
Hoppler, Stefan