FUCCI tracking shows cell-cycle-dependent Neurog3 variation in pancreatic progenitors

Matthew E. Bechard, Eric D. Bankaitis, Alessandro Ustione, David W. Piston, Mark A. Magnuson, Christopher V.E. Wright

Research output: Contribution to journalLetterpeer-review

2 Scopus citations

Abstract

During pancreas organogenesis, Neurog3HI endocrine-committing cells are generated from a population of Sox9+ mitotic progenitors with only a low level of Neurog3 transcriptional activity (Neurog3TA.LO). Low-level Neurog3 protein, in Neurog3TA.LO cells, is required to maintain their mitotic endocrine-lineage-primed status. Herein, we describe a Neurog3-driven FUCCI cell-cycle reporter (Neurog3P2A.FUCCI) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9+ Neurog3TA.LO progenitors, the majority of cells in S-G2-M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in G1 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 Neurog3TA.LO progenitors with entrance into G1 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.

Original languageEnglish
Article numbere23050
JournalGenesis
Volume55
Issue number9
DOIs
StatePublished - Sep 2017

Keywords

  • endocrine-biased
  • lineage priming
  • progenitor

Fingerprint Dive into the research topics of 'FUCCI tracking shows cell-cycle-dependent Neurog3 variation in pancreatic progenitors'. Together they form a unique fingerprint.

Cite this