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

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Balboa , D , Prasad , R B , Groop , L & Otonkoski , T 2019 , ' Genome editing of human pancreatic beta cell models : problems, possibilities and outlook ' , Diabetologia , vol. 62 , no. 8 , pp. 1329-1336 .

Title: Genome editing of human pancreatic beta cell models : problems, possibilities and outlook
Author: Balboa, Diego; Prasad, Rashmi B.; Groop, Leif; Otonkoski, Timo
Contributor organization: Centre of Excellence in Stem Cell Metabolism
Timo Pyry Juhani Otonkoski / Principal Investigator
Research Programs Unit
Faculty of Medicine
University of Helsinki
STEMM - Stem Cells and Metabolism Research Program
Centre of Excellence in Complex Disease Genetics
Institute for Molecular Medicine Finland
University Management
Helsinki One Health (HOH)
HUS Children and Adolescents
Children's Hospital
Date: 2019-08
Language: eng
Number of pages: 8
Belongs to series: Diabetologia
ISSN: 0012-186X
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.
Subject: Beta cells
Cell models
Genome editing
Human islets
Stem cells
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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