Derivation of enteric neuron lineages from human pluripotent stem cells

被引:36
作者
Barber, Kevin [1 ]
Studer, Lorenz [2 ,3 ]
Fattahi, Faranak [1 ,4 ]
机构
[1] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
[2] Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA
[3] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA
[4] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
关键词
FETAL-RAT GUT; NERVOUS-SYSTEM; CREST CELLS; IN-VITRO; DIFFERENTIATION; THERAPY; EXPRESSION; INDUCTION; DISEASE;
D O I
10.1038/s41596-019-0141-y
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The enteric nervous system (ENS) represents a vast network of neuronal and glial cell types that develops entirely from migratory neural crest (NC) progenitor cells. Considerable improvements in the understanding of the molecular mechanisms underlying NC induction and regional specification have recently led to the development of a robust method to re-create the process in vitro using human pluripotent stem cells (hPSCs). Directing the fate of hPSCs toward the enteric NC (ENC) results in an accessible and scalable in vitro model of ENS development. The application of hPSC-derived enteric neural lineages provides a powerful platform for ENS-related disease modeling and drug discovery. Here we present a detailed protocol for the induction of a regionally specific NC intermediate that occurs over the course of a 15-d interval and is an effective source for the in vitro derivation of functional enteric neurons (ENs) from hPSCs. Additionally, we introduce a new and improved protocol that we have developed to optimize the protocol for future applications in regenerative medicine, in which components of undefined activity have been replaced with fully defined culture conditions. This protocol provides access to a broad range of human ENS lineages within a 30-d period.
引用
收藏
页码:1261 / 1279
页数:19
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