Electrophysiological characterisation of iPSC-derived human β-like cells and an

Multielectrode array SLC30A8 electrical activity electrical coupling electrophysiology exocytosis hiPSC-derived Beta-like cells insulin secretion

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
18 Oct 2023
Historique:
pubmed: 31 10 2023
medline: 31 10 2023
entrez: 31 10 2023
Statut: epublish

Résumé

iPSC-derived human β-like cells (BLC) hold promise for both therapy and disease modelling, 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 BLCs functions. The Multi-Electrode Arrays (MEAs) measuring the extracellular electrical activity revealed that BLCs are electrically coupled, produce slow potential (SP) signals like primary β-cells 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. These were comparable to those in primary β and EndoC-βH1 cells. The K

Identifiants

pubmed: 37905040
doi: 10.1101/2023.10.17.561014
pmc: PMC10614917
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : UM1 DK126185
Pays : United States

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Auteurs

Manon Jaffredo (M)

University of Bordeaux, CNRS, Institute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, Pessac, France.

Nicole A J Krentz (NAJ)

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA.

Benoite Champon (B)

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Claire E Duff (CE)

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Sameena Nawaz (S)

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Nicola Beer (N)

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Christian Honore (C)

Cell Therapy R&D, Novo Nordisk A/S, 2760 Måløv, Denmark.

Anne Clark (A)

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Patrik Rorsman (P)

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Jochen Lang (J)

University of Bordeaux, CNRS, Institute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, Pessac, France.

Anna L Gloyn (AL)

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA.
Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Matthieu Raoux (M)

University of Bordeaux, CNRS, Institute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, Pessac, France.

Benoit Hastoy (B)

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Classifications MeSH