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Publication : Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

First Author  Zeng C Year  2017
Journal  Cell Metab Volume  25
Issue  5 Pages  1160-1175.e11
PubMed ID  28467932 Mgi Jnum  J:347405
Mgi Id  MGI:6106687 Doi  10.1016/j.cmet.2017.04.014
Citation  Zeng C, et al. (2017) Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal beta Cell Proliferation. Cell Metab 25(5):1160-1175.e11
abstractText  Pancreatic beta cell mass for appropriate blood glucose control is established during early postnatal life. beta 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 beta cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of beta 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 beta 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 beta cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal beta cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal beta cells and paves the way for the identification of novel therapeutic targets to stimulate beta cell regeneration.
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