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Combinatorial transcription factor profiles predict mature and functional human islet α and β cells
Shristi Shrestha, … , Alvin C. Powers, Marcela Brissova
Shristi Shrestha, … , Alvin C. Powers, Marcela Brissova
Published August 24, 2021
Citation Information: JCI Insight. 2021;6(18):e151621. https://doi.org/10.1172/jci.insight.151621.
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Resource and Technical Advance Cell biology Endocrinology Article has an altmetric score of 11

Combinatorial transcription factor profiles predict mature and functional human islet α and β cells

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Abstract

Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells, and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells coexpressing ARX/MAFB (α cells) and MAFA/MAFB (β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-Seq, MAFA/MAFB-coexpressing β cells showed enhanced electrophysiological activity. Thus, these results indicate that combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.

Authors

Shristi Shrestha, Diane C. Saunders, John T. Walker, Joan Camunas-Soler, Xiao-Qing Dai, Rachana Haliyur, Radhika Aramandla, Greg Poffenberger, Nripesh Prasad, Rita Bottino, Roland Stein, Jean-Philippe Cartailler, Stephen C.J. Parker, Patrick E. MacDonald, Shawn E. Levy, Alvin C. Powers, Marcela Brissova

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