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Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
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Human islets contain four distinct subtypes of β cells
Craig Dorrell1, Jonathan Schug2, Pamela S Canaday1
1Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Nature Communications
|July 12, 2016
Summary
Researchers discovered four distinct subtypes of human beta cells (β1-4), previously thought to be a single cell type. These subtypes have different functions and are altered in type 2 diabetes, suggesting new avenues for diabetes research.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetes Research
Background:
- Human pancreatic islets contain five endocrine cell types.
- Beta cells (β cells) produce insulin, and their dysfunction causes diabetes mellitus.
- Beta cells were previously considered a homogenous population.
Purpose of the Study:
- To identify and characterize distinct subtypes of human beta cells.
- To investigate the functional and medical relevance of beta cell heterogeneity.
- To determine if beta cell subtype distribution is altered in type 2 diabetes.
Main Methods:
- Antigenic identification of beta cell subpopulations using ST8SIA1 and CD9 expression.
- Analysis of gene expression profiles for each subtype.
- Assessment of basal and glucose-stimulated insulin secretion from each subtype.
Main Results:
- Four distinct human beta cell subtypes (β1-4) were identified based on ST8SIA1 and CD9 expression.
- These subtypes exhibit diverse gene expression and distinct insulin secretion patterns.
- Beta cell subtype distribution is significantly altered in individuals with type 2 diabetes.
Conclusions:
- Human beta cells are not homogenous but comprise at least four antigenically distinct subtypes.
- Beta cell heterogeneity is functionally relevant, impacting insulin secretion.
- Altered beta cell subtype distribution in type 2 diabetes highlights potential therapeutic targets.
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