Single-cell transcriptomics of the human endocrine pancreas

Yue J. Wang, Jonathan Schug, Kyoung Jae Won, Chengyang Liu, Ali Naji, Dana Avrahami, Maria L. Golson, Klaus H. Kaestner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that a- and β-Cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, a- and β-Cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating α-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating α-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human a-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.

Original languageAmerican English
Pages (from-to)3028-3038
Number of pages11
JournalDiabetes
Volume65
Issue number10
DOIs
StatePublished - 1 Oct 2016

Bibliographical note

Funding Information:
This study was supported by the BIRAX Regenerative Medicine Initiative (14BX14NHBG to D.A.) and the NIDDK (UC4DK104119 to K.H.K.).

Publisher Copyright:
© 2016 by the American Diabetes Association.

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