The role of DNA demethylation in liver to pancreas transdifferentiation

Adi Har-Zahav; Daniela Lixandru; David Cheishvili; Ioan Valentin Matei; Ioana Raluca Florea; Veronica Madalina Aspritoiu; Inna Blus-Kadosh; Irit Meivar-Levy; Andreea Madalina Serban; Irinel Popescu; Moshe Szyf; Sarah Ferber; Simona Olimpia Dima

doi:10.1186/s13287-022-03159-6

The role of DNA demethylation in liver to pancreas transdifferentiation

Adi Har-Zahav
, Daniela Lixandru
, David Cheishvili
, Ioan Valentin Matei
, Ioana Raluca Florea
, Veronica Madalina Aspritoiu
, Inna Blus-Kadosh
, Irit Meivar-Levy
, Andreea Madalina Serban
, Irinel Popescu
, Moshe Szyf
, Sarah Ferber
, Simona Olimpia Dima

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Background: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

Original language	English
Article number	476
Journal	Stem Cell Research and Therapy
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13287-022-03159-6
State	Published - Dec 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

This work has been supported by the Research Grants Dia-Cure P 37 794, POC-A. 1-A.1.1.4-E-2015 (2016–2020) and by The Israel Science Foundation (#1537 2016). A part of the study has been published as a Ph.D. thesis of Adi Har-Zahav. We wish to thank members of the lab and Dia-Cure team for fruitful discussions. Adi Har-Zahav (Aff 3), Ioan Valentin Matei (Aff 7), Inna Blus-Kadosh, Irit Meivar-Levy (Aff 3), and Sarah Ferber (Aff 3): Previous affiliation.

Funders	Funder number
Ioan Valentin Matei
Israel Science Foundation	1537 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cell replacement therapy for diabetes
DNA methylation
Epigenetic modifications
Liver
Pancreas
Pancreatic transcription factors
Transdifferentiation

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10.1186/s13287-022-03159-6

Cite this

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title = "The role of DNA demethylation in liver to pancreas transdifferentiation",

abstract = "Background: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.",

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doi = "10.1186/s13287-022-03159-6",

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AU - Matei, Ioan Valentin

AU - Florea, Ioana Raluca

AU - Aspritoiu, Veronica Madalina

AU - Blus-Kadosh, Inna

AU - Meivar-Levy, Irit

AU - Serban, Andreea Madalina

AU - Popescu, Irinel

AU - Szyf, Moshe

AU - Ferber, Sarah

AU - Dima, Simona Olimpia

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N2 - Background: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

AB - Background: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

KW - Cell replacement therapy for diabetes

KW - DNA methylation

KW - Epigenetic modifications

KW - Liver

KW - Pancreas

KW - Pancreatic transcription factors

KW - Transdifferentiation

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The role of DNA demethylation in liver to pancreas transdifferentiation

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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