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Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.


ABSTRACT: Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic ?- and ?-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase ?-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify ?-, ?-, and ?-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 ?- and ?-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 ?-cells. In addition, within highly purified adult glucagon-expressing ?-cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet ?- and ?-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.

SUBMITTER: Blodgett DM 

PROVIDER: S-EPMC4542439 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic α- and β-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase β-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify α-, β-, and δ-cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the subpopulations by f  ...[more]

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