GSE188827: Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells

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GROUP CONDITION SAMPLES
hiPSC-derived beta like cells at Stage7
GSM5690750 GSM5690751 GSM5690752 GSM5690757 GSM5690758 GSM5690759 GSM5690764 GSM5690765 GSM5690766 GSM5690767 GSM5690768 GSM5690769
GSM5690753 GSM5690754 GSM5690755 GSM5690756 GSM5690760 GSM5690761 GSM5690762 GSM5690763 GSM5690770 GSM5690771 GSM5690772 GSM5690773 GSM5690774 GSM5690775 GSM5690776 GSM5690777
Description

Submission Date: Nov 15, 2021

Summary: Studies of monogenic diabetes are particularly useful as we can gain insight into the molecular events of pancreatic β-cell failure. Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes form, caused by a mutation in the HNF4A gene. Human induced pluripotent stem cells (hiPSC) provide an excellent tool for disease modelling by subsequent directed differentiation toward desired pancreatic islet cells, but cellular phenotypes in terminally differentiated cells are notoriously difficult to detect. Re-creating a spatial (3D) environment may facilitate phenotype detection. In this study, we studied MODY1 using hiPSC-derived pancreatic β-like patient and isogenic control cell lines in two different 3D contexts. Using size-adjusted cell aggregates and alginate capsules we showed that the 3D context was critical to facilitate the detection of mutation-specific phenotypes. In 3D cell aggregates we identified irregular cell clusters and lower levels of structural proteins by proteome analysis, whereas in 3D alginate capsules we identified altered levels of glycolytic proteins in the glucose sensing apparatus by proteome analysis. Our study provides novel knowledge on normal and abnormal function of HNF4A paving the way for translational studies of new drug targets that can be used in precision diabetes medicine of MODY.

GEO Accession ID: GSE188827

PMID: 35043148

Description

Submission Date: Nov 15, 2021

Summary: Studies of monogenic diabetes are particularly useful as we can gain insight into the molecular events of pancreatic β-cell failure. Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes form, caused by a mutation in the HNF4A gene. Human induced pluripotent stem cells (hiPSC) provide an excellent tool for disease modelling by subsequent directed differentiation toward desired pancreatic islet cells, but cellular phenotypes in terminally differentiated cells are notoriously difficult to detect. Re-creating a spatial (3D) environment may facilitate phenotype detection. In this study, we studied MODY1 using hiPSC-derived pancreatic β-like patient and isogenic control cell lines in two different 3D contexts. Using size-adjusted cell aggregates and alginate capsules we showed that the 3D context was critical to facilitate the detection of mutation-specific phenotypes. In 3D cell aggregates we identified irregular cell clusters and lower levels of structural proteins by proteome analysis, whereas in 3D alginate capsules we identified altered levels of glycolytic proteins in the glucose sensing apparatus by proteome analysis. Our study provides novel knowledge on normal and abnormal function of HNF4A paving the way for translational studies of new drug targets that can be used in precision diabetes medicine of MODY.

GEO Accession ID: GSE188827

PMID: 35043148

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