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FUCCI tracking shows cell‐cycle‐dependent Neurog3 variation in pancreatic progenitors
Author(s) -
Bechard Matthew E.,
Bankaitis Eric D.,
Ustione Alessandro,
Piston David W.,
Magnuson Mark A.,
Wright Christopher V.E.
Publication year - 2017
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23050
Subject(s) - progenitor cell , biology , progenitor , enteroendocrine cell , cell cycle , microbiology and biotechnology , endocrine system , mitosis , gene , stem cell , genetics , endocrinology , hormone
During pancreas organogenesis, Neurog3 HI endocrine‐committing cells are generated from a population of Sox9 + mitotic progenitors with only a low level of Neurog3 transcriptional activity ( Neurog3 TA.LO ). Low‐level Neurog3 protein, in Neurog3 TA.LO cells, is required to maintain their mitotic endocrine‐lineage‐primed status. Herein, we describe a Neurog3 ‐driven FUCCI cell‐cycle reporter ( Neurog3 P2A.FUCCI ) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9 + Neurog3 TA.LO progenitors, the majority of cells in S‐G 2 ‐M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in G 1 have low Neurog3 levels with increased expression of endocrine differentiation markers. These findings support a model in which variations in Neurog3 protein levels are coordinated with cell‐cycle phase progression in Neurog3 TA.LO progenitors with entrance into G 1 triggering a concerted effort, beyond increasing Neurog3 levels, to maintain an endocrine‐lineage‐primed state by initiating expression of the downstream endocrine differentiation program prior to endocrine‐commitment.