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DNA甲基化状态与成年β细胞再生能力相关。

DNA methylation status correlates with adult β-cell regeneration capacity.

作者信息

Khurana Ishant, Al-Hasani Keith, Maxwell Scott, K N Harikrishnan, Okabe Jun, Cooper Mark E, Collombat Patrick, El-Osta Assam

机构信息

Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.

Epigenetics in Human Health and Disease Laboratory, Central Clinical School, Monash University, Melbourne, VIC, Australia.

出版信息

NPJ Regen Med. 2021 Feb 12;6(1):7. doi: 10.1038/s41536-021-00119-1.

DOI:10.1038/s41536-021-00119-1
PMID:33580013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7881134/
Abstract

The role of DNA methylation in β-cell neogenesis is poorly understood. We report that during the process of induced cell reprogramming, methylation content of the Ngn3 and Sox11 genes are diminished. These findings emphasise DNA methylation is a barrier in β-cell regeneration in adulthood, a well described pathophysiological phenomenon of major significance in explaining β-cell deficiency in diabetes in the adult pancreas.

摘要

DNA甲基化在β细胞新生中的作用尚不清楚。我们报告，在诱导细胞重编程过程中，Ngn3和Sox11基因的甲基化含量降低。这些发现强调，DNA甲基化是成年期β细胞再生的一个障碍，这是一种在解释成年胰腺糖尿病中β细胞缺乏方面具有重要意义的、已充分描述的病理生理现象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f2/7881134/2fb5a94acb84/41536_2021_119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f2/7881134/949ad740d627/41536_2021_119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f2/7881134/2fb5a94acb84/41536_2021_119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f2/7881134/949ad740d627/41536_2021_119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f2/7881134/2fb5a94acb84/41536_2021_119_Fig2_HTML.jpg

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DNA methylation status correlates with adult β-cell regeneration capacity.

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引用本文的文献

[1]
Clinical research progress on β-cell dysfunction in T2DM development in the Chinese population.

Rev Endocr Metab Disord. 2025-2

[2]
Pharmacological inhibition of human EZH2 can influence a regenerative β-like cell capacity with in vitro insulin release in pancreatic ductal cells.

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[3]
The role of DNA demethylation in liver to pancreas transdifferentiation.

Stem Cell Res Ther. 2022-9-16

[4]
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Signal Transduct Target Ther. 2022-7-22

[5]
Microencapsulation-based cell therapies.

Cell Mol Life Sci. 2022-6-8

[6]
Epigenetic Regulation of β Cell Identity and Dysfunction.

Front Endocrinol (Lausanne). 2021

本文引用的文献

[1]
Role of TET enzymes in DNA methylation, development, and cancer.

Genes Dev. 2016-4-1

[2]
The inactivation of Arx in pancreatic α-cells triggers their neogenesis and conversion into functional β-like cells.

PLoS Genet. 2013-10

[3]
Adult duct-lining cells can reprogram into β-like cells able to counter repeated cycles of toxin-induced diabetes.

Dev Cell. 2013-6-27

[4]
Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells.

Proc Natl Acad Sci U S A. 2013-5-21

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Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells.

Genome Res. 2011-9-2

[6]
Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development.

Dev Dyn. 2011-2-1

[7]
A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.

Cell Stem Cell. 2010-6-17

[8]
The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells.

Cell. 2009-8-7

[9]
Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.

Cell. 2008-1-25

[10]
The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas.

Development. 2005-7

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