Genome editing of human pancreatic beta cell models: problems, possibilities and outlook

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• dc.contributor.author Balboa, Diego
• dc.contributor.author Prasad, Rashmi B.
• dc.contributor.author Groop, Leif
• dc.contributor.author Otonkoski, Timo
• dc.date.accessioned 2019-10-29T11:00:03Z
• dc.date.available 2019-10-29T11:00:03Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.description.sponsorship The authors’ work in this area has been supported by grants from the Academy of Finland, The Novo Nordisk Foundation and the Sigrid Jusélius Foundation. TO is also funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115797 (INNODIA), which receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA), JDRF and the Leona M. and Harry B. Helmsley Charitable Trust.
• dc.format.mimetype application/pdf
• dc.identifier.citation Balboa D, Prasad RB, Groop L, Otonkoski T. Genome editing of human pancreatic beta cell models: problems, possibilities and outlook. Diabetologia. 2019; 62(8):1329-1336. DOI 10.1007/s00125-019-4908-z
• dc.identifier.doi http://dx.doi.org/10.1007/s00125-019-4908-z
• dc.identifier.issn 0012-186X
• dc.identifier.uri http://hdl.handle.net/10230/42546
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Diabetologia. 2019; 62(8):1329-1336
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115797
• dc.rights © The Author(s) 2019. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Beta cells
• dc.subject.keyword CRISPR-Cas9
• dc.subject.keyword Cell models
• dc.subject.keyword Diabetes
• dc.subject.keyword Genome editing
• dc.subject.keyword Human islets
• dc.subject.keyword Pancreas
• dc.subject.keyword Review
• dc.subject.keyword Stem cells
• dc.title Genome editing of human pancreatic beta cell models: problems, possibilities and outlook
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion