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Defining multistep cell fate decision pathways during pancreatic development at single‐cell resolution
Author(s) -
Yu XinXin,
Qiu WeiLin,
Yang Liu,
Zhang Yu,
He MaoYang,
Li LinChen,
Xu ChengRan
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100164
Subject(s) - biology , cell fate determination , progenitor cell , microbiology and biotechnology , cellular differentiation , embryonic stem cell , stem cell , lineage (genetic) , enteroendocrine cell , pancreas , developmental biology , cell , directed differentiation , organogenesis , genetics , gene , endocrine system , transcription factor , induced pluripotent stem cell , endocrinology , hormone
The generation of terminally differentiated cell lineages during organogenesis requires multiple, coordinated cell fate choice steps. However, this process has not been clearly delineated, especially in complex solid organs such as the pancreas. Here, we performed single‐cell RNA ‐sequencing in pancreatic cells sorted from multiple genetically modified reporter mouse strains at embryonic stages E9.5–E17.5. We deciphered the developmental trajectories and regulatory strategies of the exocrine and endocrine pancreatic lineages as well as intermediate progenitor populations along the developmental pathways. Notably, we discovered previously undefined programs representing the earliest events in islet α‐ and β‐cell lineage allocation as well as the developmental pathway of the “first wave” of α‐cell generation. Furthermore, we demonstrated that repressing ERK pathway activity is essential for inducing both α‐ and β‐lineage differentiation. This study provides key insights into the regulatory mechanisms underlying cell fate choice and stepwise cell fate commitment and can be used as a resource to guide the induction of functional islet lineage cells from stem cells in vitro .