Erratum: A suppressor locus for MODY3-diabetes

García-González, Miguel A.; Carette, Claire; Chiral, Magali; Makinistoglu, Munevver Parla; Garbay, Serge; Prévost, Géraldine; Madaras, Cécile; Hérault, Yann; Leibovici, Michel; Pontoglio, Marco

doi:10.1038/srep35697

Cited by 2 publications

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“…Another example is the most common form of monogenic diabetes, MODY3, caused by heterozygous mutations in the transcription factor HNF1a. Mice with heterozygous mutations in HNF1A are healthy (42) and mice with HNF1A null mutations can have a diabetic phenotype, but with significant variability dependent on genetic background (43). These results suggest that there are complex, human-specific genome-phenotype interactions that must be additionally investigated using human models.…”

Section: The Need For Human B-cell Models In Diabetes Researchmentioning

confidence: 98%

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021

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A mechanistic understanding of the genetic basis of complex diseases such as diabetes mellitus remain elusive due in large part to the activity of genetic disease modifiers that impact the penetrance and/or presentation of disease phenotypes. In the face of such complexity, rare forms of diabetes that result from single-gene mutations (monogenic diabetes) can be used to model the contribution of individual genetic factors to pancreatic β-cell dysfunction and the breakdown of glucose homeostasis. Here we review the contribution of protein coding and non-protein coding genetic disease modifiers to the pathogenesis of diabetes subtypes, as well as how recent technological advances in the generation, differentiation, and genome editing of human pluripotent stem cells (hPSC) enable the development of cell-based disease models. Finally, we describe a disease modifier discovery platform that utilizes these technologies to identify novel genetic modifiers using induced pluripotent stem cells (iPSC) derived from patients with monogenic diabetes caused by heterozygous mutations.

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Section: The Need For Human B-cell Models In Diabetes Researchmentioning

confidence: 98%

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021

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“…The detailed pathomechanisms of monogenic diabetes are not yet fully understood since mouse models do not completely recapitulate the human disease phenotype (121,144,145), and patient samples such as b-cells have very limited availability. Moreover, animal models with a specific knockout of MODY genes show speciesspecific differences that do not entirely recapitulate the patient phenotype (146)(147)(148)(149)(150). Therefore, even more suitable disease models are crucial to develop an adequate therapy.…”

Section: Modeling Pancreatic Endocrine Developmentmentioning

confidence: 99%

Human Pluripotent Stem Cells Go Diabetic: A Glimpse on Monogenic Variants

et al. 2021

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Diabetes, as one of the major diseases in industrial countries, affects over 350 million people worldwide. Type 1 (T1D) and type 2 diabetes (T2D) are the most common forms with both types having invariable genetic influence. It is accepted that a subset of all diabetes patients, generally estimated to account for 1–2% of all diabetic cases, is attributed to mutations in single genes. As only a subset of these genes has been identified and fully characterized, there is a dramatic need to understand the pathophysiological impact of genetic determinants on β-cell function and pancreatic development but also on cell replacement therapies. Pluripotent stem cells differentiated along the pancreatic lineage provide a valuable research platform to study such genes. This review summarizes current perspectives in applying this platform to study monogenic diabetes variants.

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Erratum: A suppressor locus for MODY3-diabetes

Abstract: Scientific Reports 6: Article number: 33087; published online: 26 September 2016; updated: 21 October 2016

Cited by 2 publications

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Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

Human Pluripotent Stem Cells Go Diabetic: A Glimpse on Monogenic Variants

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