Year: 2017
Type: article
Abstract: 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.
Source: genesis
DOI: 10.1002/dvg.23050
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Heart Association, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, National Institutes of Health, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, RIKEN, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, RIKEN Brain Science Institute
Awards: G1300984159, G1440127953, G2019238319, G2304076072, G2444910177, G275963511, G3036423272, G3433274139, G5853943267, G6297262231, G6379660250, G6418694057, G6741342835, G725763919, G7520984233, G7843312170, G79480885, G8239595131, Multiphoton microscope upgrade, Architecture and communication controlling the efficient generation of beta cells, G9000081609, G9000083539, Molecular and Cellular Basis for Digestive Diseases
OpenAlex ID: W2745066675