Transcription factors that shape the mammalian pancreas
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REVIEW
Transcription factors that shape the mammalian pancreas Rachel E. Jennings 1,2
&
Raphael Scharfmann 3
&
Willem Staels 3,4,5
Received: 27 February 2020 / Accepted: 3 April 2020 / Published online: 31 August 2020 # The Author(s) 2020
Abstract Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know about mammalian pancreas development stems from mouse genetics. We have learnt that a unique set of transcription factors controls endocrine and exocrine cell differentiation. Transgenic mouse models have been instrumental in studying the function of these transcription factors. Mouse and human pancreas development are very similar in many respects, but the devil is in the detail. To unravel human pancreas development in greater detail, in vitro cellular models (including directed differentiation of stem cells, human beta cell lines and human pancreatic organoids) are used; however, in vivo validation of these results is still needed. The current best ‘model’ for studying human pancreas development are individuals with monogenic forms of diabetes. In this review, we discuss mammalian pancreas development, highlight some discrepancies between mouse and human, and discuss selected transcription factors that, when mutated, cause permanent neonatal diabetes.
Keywords Development . Human . Islets of Langerhans . Mouse . Neonatal diabetes . NEUROG3 . Neurogenin 3 . Pancreas and duodenal homeobox 1 . PDX1 . Regulatory factor X6 . Review . RFX6 . Transcription factors Abbreviations ABCC8 ATP-binding cassette transporter subfamily C member 8 dpc Days post conception E Embryonic day GATA4 GATA binding protein 4 hPO Human pancreatic organoid hPSC Human pluripotent stem cell NEUROG3 Neurogenin 3 NKX6–1 NK6 homeobox 1 PDX1 Pancreatic and duodenal homeobox 1
RFX6 SOX9 wpc
Regulatory factor X6 SRY-box transcription factor 9 Weeks post conception
Scope During human pancreas development, the orchestration of differentiation fates and the acquisition of endocrine and exocrine cell identity depend on the controlled expression of unique sets of transcription factors. Transgenic mouse models
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05161-0) contains a slide of the figure for download, which is available to authorised users. * Rachel E. Jennings [email protected] * Raphael Scharfmann [email protected] * Willem Staels [email protected] 1
Division of Diabetes, Endocrinology & Gastroenterology, Faculty of Biology, Medicine & Health, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK
2
Endocrinology Department, Manchester University NHS Foundation Trust, Manchester, UK
3
Institut Cochin, INSERM, U1016, CNRS, UMR8104, Université de Paris, 75014 Paris, France
4
Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
5
Department of Pediatrics, Division of Pe
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