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

Balboa, Diego; Prasad, Rashmi B LU ; Groop, Leif LU and Otonkoski, Timo (2019) In Diabetologia 62(8). p.1329-1336
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
62
issue
8
pages
1329 - 1336
publisher
Springer
external identifiers
  • scopus:85066858770
ISSN
1432-0428
DOI
10.1007/s00125-019-4908-z
language
English
LU publication?
yes
id
24341c53-345f-4fa2-95ea-b68405796347
date added to LUP
2019-06-19 16:05:03
date last changed
2019-09-19 03:00:22
@article{24341c53-345f-4fa2-95ea-b68405796347,
  abstract     = {<p>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.</p>},
  author       = {Balboa, Diego and Prasad, Rashmi B and Groop, Leif and Otonkoski, Timo},
  issn         = {1432-0428},
  language     = {eng},
  month        = {06},
  number       = {8},
  pages        = {1329--1336},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Genome editing of human pancreatic beta cell models : problems, possibilities and outlook},
  url          = {http://dx.doi.org/10.1007/s00125-019-4908-z},
  volume       = {62},
  year         = {2019},
}