Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa
The role of targeted (epi)genetic modifications in potential diabetes therapy
2023
Authors:
Đorđević, MarijaDinić, Svetlana
Mihailović, Mirjana
Uskoković, Aleksandra
Grdović, Nevena
Arambašić Jovanović, Jelena
Vidaković, Melita
Document Type:
Book part (Published version)
,
© 2023 by the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Metadata
Show full item recordAbstract:
Diabetes is caused by a reduced number of beta cell mass, impaired functioning, or loss of beta cell
identity through the dedifferentiation process. Direct cellular reprogramming is one of the current
strategies in the potential diabetes therapy, which would replace the lack of functional beta cells and
regulate insulin levels. This research approach involves the transdifferentiation of somatic cells from
several organs into insulin-producing cells by modulating the expression pattern of transcription fac-
tors responsible for maintaining cellular identity. This chapter will present current research involving
cellular reprogramming using the new synthetic tools that have ability to introduce targeted (epi)ge-
netic modifications. Special attention will be paid to the CRISPR/Cas9 system and its modifications.
Pancreatic alpha cells represent an attractive cell source for potential diabetes therapy because they
share a common origin with beta cells, have a high level of plasticity, and provide a natural environ-
ment suitable for cell survival because of their close placement. One of the recent studies involved the
use of the EpiCRISPR system for targeted DNA methylation within the Arx gene promoter in murine
pancreatic alpha cells. The introduced changes at the epigenetic level led to the initiation of insulin
expression in the alpha cells of the mouse pancreas and the initiation of their transdifferentiation pro-
cess into insulin-producing cells.
Keywords:
CRISPR/Cas9; insulin; epigenome editing; diabetes; pancreatic alpha cells; transdifferentiationSource:
Trends in Molecular Biology, 2023, 3, 138-150Funding / projects:
- European Foundation for the Study of Diabetes EFSD: "Transdifferentiation of pancreatic alpha to beta cells via targeted epigenome editing using epi-crisprs directed dna methylation"
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)