DOI: 10.1101/474023Nov 19, 2018Paper

Prolactin Receptor Signaling Regulates a Pregnancy-Specific Transcriptional Program in Mouse Islets

BioRxiv : the Preprint Server for Biology
Mark E. PepinRonadip R Banerjee

Abstract

Pancreatic β-cells undergo profound hyperplasia during pregnancy to maintain maternal euglycemia. Failure to reprogram β-cells into a more replicative state has been found to underlie susceptibility to gestational diabetes mellitus (GDM). We recently identified a requirement for prolactin receptor (PRLR) signaling in the metabolic adaptations to pregnancy, where mice lacking β-cell PRLR (βPRLRKO) exhibit a metabolic phenotype consistent with GDM. However, the underlying transcriptional program that is responsible for the PRLR-dependent metabolic adaptations during gestation remains incompletely understood. To identify PRLR signaling gene regulatory networks and target genes within β-cells during pregnancy, we performed a transcriptomic analysis of pancreatic islets isolated from either βPRLRKO mice or littermate controls in late gestation. Gene set enrichment analysis identified Forkhead box protein M1 (Foxm1) and polycomb repressor complex 2 (PRC2) subunits, Suz12 and Ezh2, as novel candidate regulators of PRLR-dependent β-cell adaptation. GO-term pathway enrichment revealed both established and novel PRLR signaling target genes that together describe a state of increased cellular metabolism and/or proliferation. In contrast t...Continue Reading

Related Concepts

Gene Expression
Genes
Hyperplasia
Islets of Langerhans
Laboratory mice
Structure of Beta Cell of Islet
Repressor Proteins
Transcription, Genetic
Gestational Diabetes
Alpha-beta T-Cell Receptor

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