Journal article
Electrophysiological characterization of inducible pluripotent stem cell-derived human β-like cells and an SLC30A8 disease model
- Abstract:
- Inducible pluripotent stem cell-derived human β-like cells (BLCs) hold promise for both therapy and disease modeling, but their generation remains challenging and their functional analyses beyond transcriptomic and morphological assessments remain limited. Here, we validate an approach using multicellular and single-cell electrophysiological tools to evaluate function of BLCs from pioneer protocols that can be easily adapted to more differentiated BLCs. The multi-electrode arrays (MEAs) measuring the extracellular electrical activity revealed that BLCs, like primary β-cells, are electrically coupled and produce slow potential (SP) signals that are closely linked to insulin secretion. We also used high-resolution single-cell patch clamp measurements to capture the exocytotic properties, and characterize voltage-gated sodium and calcium currents, and found that they were comparable with those in primary β- and EndoC-βH1 cells. The KATP channel conductance is greater than in human primary β-cells, which may account for the limited glucose responsiveness observed with MEA. We used MEAs to study the impact of the type 2 diabetes-protective SLC30A8 allele (p.Lys34Serfs50*) and found that BLCs with this allele have stronger electrical coupling activity. Our data suggest that BLCs can be used to evaluate the functional impact of genetic variants on β-cell function and coupling.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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Authors
+ National Institutes of Health
More from this funder
- Funder identifier:
- https://ror.org/01cwqze88
- Grant:
- UM-1DK126185
+ Agence Nationale de la Recherche
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- Funder identifier:
- https://ror.org/00rbzpz17
- Grant:
- 18-CE17-0005
+ European Foundation for the Study of Diabetes
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- Funder identifier:
- https://ror.org/05tgz4m05
- Programme:
- Albert Renold award
- Publisher:
- American Diabetes Association
- Journal:
- Diabetes More from this journal
- Volume:
- 73
- Issue:
- 8
- Pages:
- 1255-1265
- Place of publication:
- United States
- Publication date:
- 2024-05-22
- Acceptance date:
- 2024-05-05
- DOI:
- EISSN:
-
1939-327X
- ISSN:
-
0012-1797
- Pmid:
-
38985991
- Language:
-
English
- Pubs id:
-
2002797
- Local pid:
-
pubs:2002797
- Source identifiers:
-
W4399071554
- Deposit date:
-
2026-05-12
- ARK identifier:
Terms of use
- Copyright holder:
- American Diabetes Association
- Copyright date:
- 2024
- Rights statement:
- ©2024 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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