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

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Item Type:	Article
Title:	Pseudotemporal ordering of single cells reveals metabolic control of postnatal ß cell proliferation
Creators Name:	Zeng, C., Mulas, F., Sui, Y., Guan, T., Miller, N., Tan, Y., Liu, F., Jin, W., Carrano, A.C., Huising, M.O., Shirihai, O.S., 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
ISSN:	1550-4131
Publisher:	Cell Press
Volume:	25
Number:	5
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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