Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Trends Cell Biol. 2022 Feb;32(2):151-164. doi: 10.1016/j.tcb.2021.09.002. Epub 2021 Oct 1.
The endoderm, one of the three primary germ layers, gives rise to lung, liver, stomach, intestine, colon, pancreas, bladder, and thyroid. These endoderm-originated organs are subject to many life-threatening diseases. However, primary cells/tissues from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells (hPSCs), therefore, hold great promise for generating endodermal cells and their derivatives for the development of new therapeutics against these human diseases. Although a wealth of research has provided crucial information on the mechanisms underlying endoderm differentiation from hPSCs, increasing evidence has shown that metabolism, in connection with epigenetics, actively regulates endoderm differentiation in addition to the conventional endoderm inducing signals. Here we review recent advances in metabolic and epigenetic regulation of endoderm differentiation.
内胚层是三个主要的胚层之一,它分化为肺、肝、胃、肠、结肠、胰腺、膀胱和甲状腺。这些内胚层起源的器官易患许多危及生命的疾病。然而,内胚层器官的原代细胞/组织通常难以在体外生长。人多能干细胞(hPSCs)因此为生成内胚层细胞及其衍生物以开发针对这些人类疾病的新疗法提供了巨大的希望。尽管大量研究提供了关于 hPSCs 中内胚层分化的机制的重要信息,但越来越多的证据表明,代谢与表观遗传一起,除了传统的内胚层诱导信号外,还积极调节内胚层分化。在这里,我们综述了代谢和表观遗传调控内胚层分化的最新进展。