Isogenic Cellular Systems Model the Impact of Genetic Risk Variants in the Pathogenesis of Type 1 Diabetes

Frontiers in Endocrinology
Mark A WalletTodd M Brusko

Abstract

At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D). The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tolerance to β cell antigens. Early efforts to link specific risk variants with functional alterations in host immune responses have employed animal models or genotype-selected individuals from clinical bioresource banks. While some notable genotype:phenotype associations have been described, there remains an urgent need to accelerate the discovery of causal variants and elucidate the molecular mechanisms by which susceptible alleles alter immune functions. One significant limitation has been the inability to study human T1D risk loci on an isogenic background. The advent of induced pluripotent stem cells (iPSCs) and genome-editing technologies have made it possible to address a number of these outstanding questions. Specifically, the ability to drive multiple cell fates from iPSC under isogenic conditions now facilitates the analysis of causal variants in multiple cellular lineages. Bioinformatic analyses have reveal...Continue Reading

References

Jun 1, 1987·The Journal of Experimental Medicine·L S WickerM C Appel
Sep 13, 1969·British Medical Journal·D R GambleK W Taylor
Sep 13, 1969·British Medical Journal·D R Gamble, K W Taylor
Feb 1, 1981·Diabetologia·A H BarnettD A Pyke
Jan 1, 1995·Annual Review of Immunology·L S WickerL B Peterson
May 1, 1994·Clinical Immunology and Immunopathology·K J PennlineM Monahan
Jul 31, 2001·Lancet·M A Atkinson, G S Eisenbarth
Jan 31, 2002·Arthritis and Rheumatism·Gerald T NepomWilliam W Kwok
Apr 30, 2003·Diabetes·Polly J BingleyPatricia W Mueller
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kevin S GoudyMark A Atkinson
Sep 4, 2003·Genome Research·Paul D ThomasApurva Narechania
Dec 18, 2003·Annals of the New York Academy of Sciences·George S Eisenbarth
Mar 24, 2004·Seminars in Immunology·Jason D Fontenot, Alexander Y Rudensky
Aug 23, 2005·Immunity·Mark S AndersonDiane Mathis
Nov 2, 2005·The Journal of Experimental Medicine·Stuart I ManneringAnthony W Purcell
Aug 10, 2006·Plant Physiology·Aleel K Grennan
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Jul 12, 2007·The Journal of Biological Chemistry·Ken NishimuraMahito Nakanishi
May 1, 2008·Current Diabetes Reports·Peter AchenbachUNKNOWN Pre-POINT Study Group
Dec 26, 2008·The New England Journal of Medicine·Maria J RedondoTihamer Orban
Mar 19, 2009·Journal of Leukocyte Biology·Sigal GeryH Phillip Koeffler
May 12, 2009·Nature Genetics·Jeffrey C BarrettUNKNOWN Type 1 Diabetes Genetics Consortium
Jan 12, 2010·Diabetologia·R GiananiG S Eisenbarth
Apr 24, 2010·Immunity·Eystein S Husebye, Mark S Anderson
May 1, 2010·Nature·Jeffrey A BluestoneGeorge Eisenbarth
May 12, 2010·The Journal of Clinical Investigation·Alexey BersenevWei Tong
May 25, 2010·Seminars in Immunopathology·Patrick A RoweMark A Atkinson

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Citations

Jul 17, 2019·Clinical and Experimental Immunology·L PetersT M Brusko
Jan 24, 2021·Immunology and Cell Biology·Melanie R ShapiroTodd M Brusko
Jul 25, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel J PerryTodd M Brusko

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Methods Mentioned

BETA
biopsy
transgenic
lavage
gene

Software Mentioned

ReproTeSR
SnapGene
GeneVisible
Protein ANalysis THrough Evolutionary Relationships ontology

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