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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)3028-3038
Number of pages11
JournalDiabetes
Volume65
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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