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Pseudotemporal ordering of single cells reveals metabolic control of postnatal ß cell proliferation

Item Type:Article
Title:Pseudotemporal ordering of single cells reveals metabolic control of postnatal ß cell proliferation
Creators Name:Zeng, C. and Mulas, F. and Sui, Y. and Guan, T. and Miller, N. and Tan, Y. and Liu, F. and Jin, W. and Carrano, A.C. and Huising, M.O. and Shirihai, O.S. and Yeo, G.W. and Sander, M.
Abstract:Pancreatic β cell mass for appropriate blood glucose control is established during early postnatal life. β cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of β cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of β cells from multiple postnatal time points and ordered cells based on transcriptional similarity using a new analytical tool. This analysis captured signatures of immature, proliferative β cells and established high expression of amino acid metabolic, mitochondrial, and Srf/Jun/Fos transcription factor genes as their hallmark feature. Experimental validation revealed high metabolic activity in immature β cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal β cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal β cells and paves the way for the identification of novel therapeutic targets to stimulate β cell regeneration.
Keywords:Beta Cell, Single-Cell RNA-Seq, Proliferation, Reactive Oxygen Species, Amino Acid Metabolism, Transcription Factor, Srf, Mitochondrial, Oxidative Phosphorylation, Catalase, Animals, Mice
Source:Cell Metabolism
Publisher:Cell Press
Page Range:1160-1175.e11
Date:2 May 2017
Additional Information:Copyright © 2017 Elsevier Inc. All rights reserved.
Official Publication:https://doi.org/10.1016/j.cmet.2017.04.014
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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