Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets
AuthorsBlodgett, David M.
Cura, Anthony J.
Kennedy, Norman J.
Davis, Roger J.
Kent, Sally C
Greiner, Dale L.
Harlan, David M.
diLorio, Philip J. Jr.
UMass Chan AffiliationsProgram in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Program in Molecular Medicine
Diabetes Center of Excellence
Department of Medicine
Document TypeJournal Article
Endocrinology, Diabetes, and Metabolism
MetadataShow full item record
AbstractUnderstanding 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. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Diabetes. 2015 Sep;64(9):3172-81. doi: 10.2337/db15-0039. Epub 2015 Apr 30. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/25935