Reconstructing human pancreatic differentiation by mapping specific cell populations during development
Reconstructing human pancreatic differentiation by mapping specific cell populations during development
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DOI：
10.7554/elife.27564
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发表时间：
2017-07-21
期刊：
影响因子：
7.7
通讯作者：
Scharfmannt, Raphael
中科院分区：
文献类型：
--
作者：
Ramond, Cyrille;Glaser, Nicolas;Scharfmannt, Raphael
与动物模型相比，关于人类发育的信息仍然很少。在这里，我们使用细胞表面标记物重建了人胎儿胰腺分化。我们证明，在发育7周时，糖蛋白2(GP2)标志着一个多能细胞群，它将分化为腺泡、导管或内分泌谱系。腺泡谱系的发展与GP2表达的增加是平行的。相反，GP2群体中的一个子集通过下调GP2和CD142并打开内分泌分化的标志物NEUROG3来经历内分泌分化。内分泌成熟通过上调SUSD2和降低ECAD水平来进行。最后，来自人类多能干细胞的胰腺内分泌细胞的体外分化模拟了体内的关键事件。我们的工作为扩大我们对成熟人类胰腺细胞类型的起源以及这种谱系决定是如何调控的理解铺平了道路。
Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2 population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.