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

Chun Zeng, Francesca Mulas, Yinghui Sui, Tiffany Guan, Nathanael Miller, Yuliang Tan, Fenfen Liu, Wen Jin, Andrea C. Carrano, Mark O. Huising, Orian S. Shirihai, Gene W. Yeo, Maike Sander

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1160-1175.e11
JournalCell Metabolism
Volume25
Issue number5
DOIs
StatePublished - May 2 2017

Keywords

  • amino acid metabolism
  • beta cell
  • catalase
  • mitochondrial
  • oxidative phosphorylation
  • proliferation
  • reactive oxygen species
  • single-cell RNA-seq
  • Srf
  • transcription factor

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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