| 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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