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^*

^*Corresponding author for this work

Dia-Cure, Acad. Nicolae Cajal Institute of Medical Scientific Research, Titu Maiorescu University, Bucharest, Romania.
Systems Biology of Aging Group, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania.
Institute of Gastroenterology, Hepatology and Nutrition, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler School of Medicine, Felsenstein Medical Research Center, Tel Aviv University, Tel Aviv, Israel
The Sheba Regenerative Medicine, Stem Cell and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel
Carol Davila University of Medicine and Pharmacy Bucharest, Romania
Department of Oncology, McGill University, Montreal, QC, Canada.
HKG Epitherapeutics, Honk Kong, China
Biology and Biochemistry Department, Faculty of Biology, University of Bucharest, Bucharest, Romania
Orgenesis Ltd, Ness Ziona, Israel.
Centre of Excelence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania.

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

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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
Pages (from-to)	476-487
Number of pages	11
Journal	Stem Cell Research and Therapy
Volume	13
Early online date	16 Sept 2022
DOIs	https://doi.org/10.1186/s13287-022-03159-6
Publication status	Published - 16 Sept 2022
Externally published	Yes

Keywords

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

UN SDGs

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

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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.",

keywords = "Cell replacement therapy for diabetes, DNA methylation, Epigenetic modifications, Liver, Pancreas, Pancreatic transcription factors, Transdifferentiation",

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

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

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T1 - The role of DNA demethylation in liver to pancreas transdifferentiation

AU - Har-Zahav, Adi

AU - Lixandru, Daniela

AU - Cheishvili, David

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

PY - 2022/9/16

Y1 - 2022/9/16

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

U2 - 10.1186/s13287-022-03159-6

DO - 10.1186/s13287-022-03159-6

M3 - Article (journal)

SN - 1757-6512

VL - 13

SP - 476

EP - 487

JO - Stem Cell Research and Therapy

JF - Stem Cell Research and Therapy

ER -

The role of DNA demethylation in liver to pancreas transdifferentiation

Abstract

Keywords

UN SDGs

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