Division of Cardiology, Department of Medicine, Institute for Cell Engineering, Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Division of Cardiology, Department of Medicine, Institute for Cell Engineering, Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):256-260. doi: 10.1016/j.bbrc.2018.04.054. Epub 2018 Apr 13.
Proper control of multipotent/stem cell number and fate is essential for ensuing organ formation during development. β1-integrin, a subfamily of cell surface receptors, has a conserved role in maintenance of multipotent/stem cells, including renal progenitor cells, follicle stem cells, epidermal stem cells and neural stem cells. However, it remains unclear whether β1-integrin has a role in cardiac progenitor cell (CPC) development. Here we show that a mesodermal deletion of β1-integrin decreases Isl1 cell number in the second pharyngeal arch (PA2), where CPCs undergo renewal and expansion. Mesp1 lineage-specific mosaicism revealed that β1-integrin-deleted Isl1 cells do not proliferate in the PA2. Consistently, β1-integrin-deleted Isl1 CPCs failed to expand in vitro, independent of PA2 cells. β1-integrin co-localized and physically associated with Numb, a crucial regulator of CPC renewal and expansion. Importantly, Numb/Numbl-deleted CPCs showed dramatic reduction in β1-integrin levels. These findings suggest that β1-integrin is a key mediator of the Numb pathway in CPC maintenance.
多能/干细胞数量和命运的适当控制对于发育过程中器官的形成至关重要。β1-整联蛋白是细胞表面受体的一个亚家族，在维持多能/干细胞中具有保守作用，包括肾祖细胞、卵泡干细胞、表皮干细胞和神经干细胞。然而，β1-整联蛋白是否在心脏祖细胞 (CPC) 的发育中发挥作用尚不清楚。在这里，我们发现中胚层缺失β1-整联蛋白会减少第二咽弓 (PA2) 中的 Isl1 细胞数量，CPC 在 PA2 中经历更新和扩增。Mesp1 谱系特异性嵌合体显示，β1-整联蛋白缺失的 Isl1 细胞在 PA2 中不会增殖。一致地，β1-整联蛋白缺失的 Isl1 CPC 在体外未能扩增，与 PA2 细胞无关。β1-整联蛋白与 Numb 共定位并物理相关，Numb 是 CPC 更新和扩增的关键调节因子。重要的是，Numb/Numbl 缺失的 CPC 显示β1-整联蛋白水平显著降低。这些发现表明，β1-整联蛋白是 CPC 维持中 Numb 途径的关键介质。
