Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, 2200 Denmark.
Semin Cell Dev Biol. 2019 Aug;92:77-88. doi: 10.1016/j.semcdb.2018.08.008. Epub 2018 Aug 25.
The pancreas is a compound gland comprised of both exocrine acinar and duct cells as well as endocrine islet cells. Most notable amongst the latter are the insulin-synthesizing β-cells, loss or dysfunction of which manifests in diabetes mellitus. All exocrine and endocrine cells derive from multipotent pancreatic progenitor cells arising from the primitive gut epithelium via inductive interactions with adjacent mesodermal tissues. Research in the last two decades has revealed the identity of many of these extrinsic cues and they include signaling molecules used in many other developmental contexts such as retinoic acid, fibroblast growth factors, and members of the TGF-β superfamily. As important as these inductive cues is the absence of other signaling molecules such as hedgehog family members. Much has been learned about the interactions of extrinsic factors with fate regulators intrinsic to the pancreatic endoderm. This new knowledge has had tremendous impact on the development of directed differentiation protocols for converting pluripotent stem cells to β-cells in vitro.
胰腺是一种复合腺体，由外分泌腺泡和导管细胞以及内分泌胰岛细胞组成。在后一种细胞中，最引人注目的是胰岛素合成的β细胞，其丧失或功能障碍表现为糖尿病。所有的外分泌和内分泌细胞都来源于多能胰腺祖细胞，这些祖细胞起源于原始肠道上皮，通过与相邻中胚层组织的诱导相互作用而产生。在过去的二十年中，研究已经揭示了其中许多外在线索的身份，它们包括在许多其他发育环境中使用的信号分子，如视黄酸、成纤维细胞生长因子和 TGF-β 超家族成员。与这些诱导线索同样重要的是，缺乏其他信号分子，如 hedgehog 家族成员。人们已经了解了外在因素与胰腺内胚层固有命运调节剂之间的相互作用。这些新知识对体外将多能干细胞定向分化为β细胞的分化方案的发展产生了巨大影响。
