Journal
DIABETES
Volume 64, Issue 9, Pages 3172-3181Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db15-0039
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Funding
- National Institutes of Health [U01-DK-089572, UC4-DK-104218]
- William and Doris Krupp Chair in Medicine
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Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic alpha-and beta-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase beta-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify alpha-, beta-, and delta-cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the subpopulations by flow cytometry, and, using next-generation RNA sequencing, we report the detailed transcriptomes of fetal and adult alpha- and beta-cells. We observed that human islet composition was not influenced by age, sex, or BMI, and transcripts for inflammatory gene products were noted in fetal beta-cells. In addition, within highly purified adult glucagon-expressing alpha-cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet alpha- and beta-cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes.
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