An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells
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Originalsprog | Engelsk |
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Tidsskrift | Cell Stem Cell |
Vol/bind | 30 |
Udgave nummer | 1 |
Sider (fra-til) | 38-51.e8 |
Antal sider | 23 |
ISSN | 1934-5909 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank Jette Larsen and Diana Klüver for technical support in the tissue culture and wet lab and Anna Månsson for technical support with the animal experiments. We thank Gelo de la Cruz and Paul van Dieken for technical support with flow cytometry, Jutta Bulkescher and Jes Dreier for technical support with fluorescence microscopy and image analysis, and Helen Neil for technical support with RNA sequencing. We acknowledge Karen Schachter for her scientific discussion and contributions to protein quantifications. We thank Päivi Miettinen for supervision of Iina Elfving and discussions about clinical features of mutation carriers in MODY genes and CHI. We also thank Hindrik Mulder and Isabella Artner for valuable discussions of MODY3 disease mechanisms. This work was supported by the Lund Stem Cell Center, Stem Therapy, Lund University, the Helmholtz Zentrum München, the Danish Council for Independent Research, Medical Sciences (grant number 8020-00254B), and the Novo Nordisk Foundation Center for Stem Cell Biology, University of Copenhagen. M.F.K. and H.S. conceived the project. M.F.K. F.M.H. and H.S. designed the experiments and interpreted the data. M.F.K. and F.M.H. performed the majority of the experiments and analyses. Individual contributions were as follows: C.T performed the NEUROD1 knockdown experiment and the GSIS experiment with calcium depletion and supported extensively with the manuscript revisions. U.T. generated the second isogenic set of cell lines and designed the illustrations for the manuscript figures; A.J. helped design the in vivo transplantation experiments, performed dissections of the mice and immunostainings and quantifications of the grafts, and contributed to data discussion; L.R.O. performed all the bioinformatics analysis; P.-O.C. obtained dermal fibroblasts from MODY3 patient, and M.K. performed reprogramming of the fibroblasts from the MODY3 donor; I.M.E. J.L.T.K. and T.T. performed the birth weight analysis and contributed with discussions on the clinical features of mutation carriers in MODY genes and MODY patients; I.N. supervised the calcium imaging experiments. M.F.K. F.M.H. and H.S. wrote the manuscript. All authors reviewed, edited, and approved the manuscript. The authors declare no competing interests.
Funding Information:
We thank Jette Larsen and Diana Klüver for technical support in the tissue culture and wet lab and Anna Månsson for technical support with the animal experiments. We thank Gelo de la Cruz and Paul van Dieken for technical support with flow cytometry, Jutta Bulkescher and Jes Dreier for technical support with fluorescence microscopy and image analysis, and Helen Neil for technical support with RNA sequencing. We acknowledge Karen Schachter for her scientific discussion and contributions to protein quantifications. We thank Päivi Miettinen for supervision of Iina Elfving and discussions about clinical features of mutation carriers in MODY genes and CHI. We also thank Hindrik Mulder and Isabella Artner for valuable discussions of MODY3 disease mechanisms. This work was supported by the Lund Stem Cell Center , Stem Therapy , Lund University , the Helmholtz Zentrum München , the Danish Council for Independent Research, Medical Sciences (grant number 8020-00254B ), and the Novo Nordisk Foundation Center for Stem Cell Biology , University of Copenhagen .
Publisher Copyright:
© 2022 The Author(s)
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