Yu-Ping Yang
Instructor
Last active: 8/28/2017

Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

Bechard ME, Bankaitis ED, Hipkens SB, Ustione A, Piston DW, Yang YP, Magnuson MA, Wright CV
Genes Dev. 2016 30 (16): 1852-65

PMID: 27585590 · PMCID: PMC5024683 · DOI:10.1101/gad.284729.116

The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

© 2016 Bechard et al.; Published by Cold Spring Harbor Laboratory Press.

MeSH Terms (11)

Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Proliferation Endocrine Cells Gene Expression Regulation, Developmental Mice Mitosis Nerve Tissue Proteins Pancreas Stem Cells

Connections (6)

This publication is referenced by other Labnodes entities:

Links