Journal
DIABETES
Volume 65, Issue 10, Pages 3028-3038Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db16-0405
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Funding
- BIRAX Regenerative Medicine Initiative [14BX14NHBG]
- NIDDK [UC4DK104119]
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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 b-cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, a-and b-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 a-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating a-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.
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