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Diabetes. 2016 Oct;65(10):3028-38. doi: 10.2337/db16-0405. Epub 2016 Jun 30.

Single-Cell Transcriptomics of the Human Endocrine Pancreas.

Author information

1
Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
2
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
3
Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel kaestner@mail.med.upenn.edu dana.tzfati@mail.huji.ac.il mgolson@mail.med.upenn.edu.
4
Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA kaestner@mail.med.upenn.edu dana.tzfati@mail.huji.ac.il mgolson@mail.med.upenn.edu.

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 α- and β-cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, α- 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 α-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.

PMID:
27364731
PMCID:
PMC5033269
DOI:
10.2337/db16-0405
[Indexed for MEDLINE]
Free PMC Article

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