Insulin-expressing cells that have been differentiated from human pluripotent stem cells in vitro lack the glucose responsiveness characteristic of mature beta cells. Beta-cell maturation in mice was studied to find genetic markers that enable screens for factors that induce bona fide beta cells in vitro. We find that functional beta-cell maturation is marked by an increase in the glucose threshold for insulin secretion and by expression of the gene urocortin 3.
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Gene Expression Omnibus
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We thank W. Vale (Salk Institute) for providing anti-human Ucn3 antibody, K. Blum for writing the MATLAB BioGUI for analysis of GSIS, A. Kweudjeu for help with transcriptional arrays, C. Honore for help with FACS analyses, A. Roose, A. Cheng and F. Deng for excellent technical assistance, and D. Cohen, Y. Mayshar and F. Pagliuca for critical reading of the manuscript. We are grateful to all members of the Melton laboratory and the Harvard Medical School Critical Discussion Group for helpful discussions and experimental advice. B.B. was supported by European Molecular Biology Organization and Juvenile Diabetes Research Foundation post-doctoral fellowships. D.A.M. is an Investigator of the Howard Hughes Medical Institute.
A.Z. is an employee of BetaLogics, a division of Janssen Research & Development, LLC, one of the Johnson & Johnson Family of Companies, Raritan, NJ, USA.
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Blum, B., Hrvatin, S., Schuetz, C. et al. Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3. Nat Biotechnol 30, 261–264 (2012). https://doi.org/10.1038/nbt.2141
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