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CD177+前定形内胚层细胞可产生胰腺β细胞
2020-04-28 14:23

德国亥姆霍兹糖尿病中心Heiko Lickert研究组发现,CD177+前定形内胚层细胞可以产生胰腺β细胞。这一研究成果在线发表于2020年4月27日的《自然—生物技术》。

体外将人多能干细胞分化为胰腺和肝脏细胞的方法,受到无法鉴定和分离内胚层中这两个器官特异不同亚群细胞的限制。

研究人员发现胰腺和肝祖细胞可以使用表面标记CD177 / NB1糖蛋白和诱导性T细胞共刺激配体CD275 / ICOSL分离,它们分别来自人多能干细胞看似均质的定形内胚层。

利用CD177和CD275分离的前定形内胚层(ADE)亚群具有典型和非典型WNT信号的反向激活。CD177+ ADE表达并合成分泌的WNT、NODAL和BMP拮抗剂CERBERUS1,从而调控胰腺命运决定。CD275+ ADE接收典型Wnt信号的调控从而分化为肝细胞。

与来自未分类分化培养的细胞相比,离体的CD177+ ADE在体外可更均匀地分化为胰腺祖细胞和功能更成熟的对葡萄糖反应的β样细胞。

附:英文原文

Title: Generation of pancreatic β cells from CD177 + anterior definitive endoderm

Author: Pallavi U. Mahaddalkar, Katharina Scheibner, Sandra Pfluger, Ansarullah, Michael Sterr, Julia Beckenbauer, Martin Irmler, Johannes Beckers, Sebastian Knbel, Heiko Lickert

Issue&Volume: 2020-04-27

Abstract: Methods for differentiating human pluripotent stem cells to pancreatic and liver lineages in vitro have been limited by the inability to identify and isolate distinct endodermal subpopulations specific to these two organs. Here we report that pancreatic and hepatic progenitors can be isolated using the surface markers CD177/NB1 glycoprotein and inducible T-cell costimulatory ligand CD275/ICOSL, respectively, from seemingly homogeneous definitive endoderm derived from human pluripotent stem cells. Anterior definitive endoderm (ADE) subpopulations identified by CD177 and CD275 show inverse activation of canonical and noncanonical WNT signaling. CD177+ ADE expresses and synthesizes the secreted WNT, NODAL and BMP antagonist CERBERUS1 and is specified toward the pancreatic fate. CD275+ ADE receives canonical Wnt signaling and is specified toward the liver fate. Isolated CD177+ ADE differentiates more homogeneously into pancreatic progenitors and into more functionally mature and glucose-responsive β-like cells in vitro compared with cells from unsorted differentiation cultures.

DOI: 10.1038/s41587-020-0492-5

Source: https://www.nature.com/articles/s41587-020-0492-5

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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