Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines.
Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines.
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DOI：
10.1016/j.stemcr.2015.02.017
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发表时间：
2015-04-14
影响因子：
5.9
通讯作者：
Keller, Gordon
中科院分区：
文献类型：
--
作者：
Nostro, M. Cristina;Sarangi, Farida;Yang, Chaoxing;Holland, Andrew;Elefanty, Andrew G.;Stanley, Edouard G.;Greiner, Dale L.;Keller, Gordon
人类多能干细胞（hPSC）代表了用于基础研究和治疗应用的胰腺β细胞的可再生来源。鉴于这种突出的潜力，已经做出了重大努力来鉴定在hPSC分化培养物中调节胰腺发育的信号传导途径。在这项研究中，我们证明了表皮生长因子（EGF）和烟酰胺信号传导的组合诱导了来自所有测试的hPSC系的NKX 6 -1+祖细胞的产生。此外，我们发现NKX 6 -1+群体的大小受维甲酸、成纤维细胞生长因子10（FGF 10）、骨形态发生蛋白（BMP）和hedgehog信号通路抑制剂治疗持续时间的调节。当移植到NOD scid gamma（NSG）受体中时，这些祖细胞分化产生外分泌和内分泌细胞，包括单激素胰岛素+细胞。总之，这些发现提供了一种有效且可重复的策略，用于产生高度富集的hPSC衍生β细胞祖细胞群体，以用于旨在进一步表征其体内发育潜力并破译调节其体外成熟的途径的研究。EGF和烟酰胺从hPSC衍生的内胚层诱导NKX 6 - 1+祖细胞NKX 6 - 1+祖细胞的产生可以通过阶段3处理的持续时间来控制多激素细胞的产生依赖于hedgehog信号传导抑制NKX 6 -1+祖细胞在体内产生导管、腺泡和内分泌细胞在这篇文章中，Nostro及其同事证明，EGF和烟酰胺信号传导诱导从多个hESC和hiPSC系有效产生NKX 6 -1+胰腺祖细胞。移植后，这些细胞产生所有胰腺谱系。这些发现提供了用于产生hPSC衍生的胰腺祖细胞的富集群体的有效且可再现的策略。
Human pluripotent stem cells (hPSCs) represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF) and nicotinamide signaling induces the generation of NKX6-1+ progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1+ population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10), and inhibitors of bone morphogenetic protein (BMP) and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG) recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin+ cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro. EGF and nicotinamide induce NKX6-1+ progenitors from hPSC-derived endoderm NKX6-1+ progenitor generation can be controlled by the duration of stage 3 treatment The generation of polyhormonal cells is dependent on hedgehog signaling inhibition NKX6-1+ progenitors give rise to ductal, acinar, and endocrine cells in vivo In this article, Nostro and colleagues demonstrate that EGF and nicotinamide signaling induces the efficient generation of NKX6-1+ pancreatic progenitors from multiple hESC and hiPSC lines. Upon transplantation, these cells give rise to all pancreatic lineages. These findings provide an efficient and reproducible strategy for generating enriched populations of hPSC-derived pancreatic progenitors.
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影响因子：
64.8
作者：
MIETTINEN, PJ;BERGER, JE;DERYNCK, R
通讯作者：
DERYNCK, R
DOI：
10.1073/pnas.0405776102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Haumaitre, C;Barbacci, E;Cereghini, S
通讯作者：
Cereghini, S
影响因子：
46.9
作者：
Gouon-Evans, Valerie;Boussemart, Lise;Keller, Gordon
通讯作者：
Keller, Gordon
影响因子：
5.2
作者：
Jiang, Jianjie;Au, Melinda;Majumdar, Anish S.
通讯作者：
Majumdar, Anish S.
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.