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Genome editing of h...
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Balboa, DiegoBarcelona Institute of Science and Technology,University of Helsinki
(author)
Genome editing of human pancreatic beta cell models : problems, possibilities and outlook
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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2019-06-03
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Springer Science and Business Media LLC,2019
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LIBRIS-ID:oai:lup.lub.lu.se:24341c53-345f-4fa2-95ea-b68405796347
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https://lup.lub.lu.se/record/24341c53-345f-4fa2-95ea-b68405796347URI
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https://doi.org/10.1007/s00125-019-4908-zDOI
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Language:English
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Summary in:English
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Subject category:for swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Understanding the molecular mechanisms behind beta cell dysfunction is essential for the development of effective and specific approaches for diabetes care and prevention. Physiological human beta cell models are needed for this work. We review the possibilities and limitations of currently available human beta cell models and how they can be dramatically enhanced using genome-editing technologies. In addition to the gold standard, primary isolated islets, other models now include immortalised human beta cell lines and pluripotent stem cell-derived islet-like cells. The scarcity of human primary islet samples limits their use, but valuable gene expression and functional data from large collections of human islets have been made available to the scientific community. The possibilities for studying beta cell physiology using immortalised human beta cell lines and stem cell-derived islets are rapidly evolving. However, the functional immaturity of these cells is still a significant limitation. CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) has enabled precise engineering of specific genetic variants, targeted transcriptional modulation and genome-wide genetic screening. These approaches can now be exploited to gain understanding of the mechanisms behind coding and non-coding diabetes-associated genetic variants, allowing more precise evaluation of their contribution to diabetes pathogenesis. Despite all the progress, genome editing in primary pancreatic islets remains difficult to achieve, an important limitation requiring further technological development.
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Prasad, Rashmi BLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)med-rpa
(author)
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Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr
(author)
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Otonkoski, TimoHelsinki University Central Hospital,University of Helsinki
(author)
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Barcelona Institute of Science and TechnologyUniversity of Helsinki
(creator_code:org_t)
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In:Diabetologia: Springer Science and Business Media LLC62:8, s. 1329-13361432-04280012-186X
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