Related Experiment Video
Updated: Jun 2, 2026
08:03
The Detection of 5-Hydroxymethylcytosine in Neural Stem Cells and Brains of Mice
Published on: September 19, 2019
DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs
Ah-Young So1, Ji-Won Jung, Seunghee Lee
1Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Plos One
|May 17, 2011
Summary
Inhibiting DNA methyltransferases (DNMTs) in stem cells triggers cellular senescence by altering gene expression and histone modifications. This epigenetic reprogramming impacts key senescence markers and microRNA regulation.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Cancer Research
Background:
- Epigenetic mechanisms, including DNA methylation, are crucial for regulating gene expression and cellular processes like senescence.
- Cancer cells utilize epigenetic regulation to control gene expression and promote survival.
Purpose of the Study:
- To investigate the role of DNA methyltransferases (DNMTs) in the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs).
- To elucidate the epigenetic changes induced by DNMT inhibition in hUCB-MSCs.
Main Methods:
- Inhibition of DNMTs using 5-azacytidine (5-AzaC) or small interfering RNA (siRNA) targeting DNMT1 and DNMT3b.
- Analysis of cellular senescence markers (p16INK4A, p21CIP1/WAF1) and histone modifications.
- Assessment of DNA methylation status at promoter regions and EZH2 enrichment.
- Evaluation of Polycomb-group (PcG) protein and microRNA (miRNA) expression levels.
Main Results:
- DNMT inhibition induced cellular senescence in hUCB-MSCs, increasing p16INK4A and p21CIP1/WAF1 expression.
- DNMT inhibition led to active histone marks and decreased CpG island methylation at p16INK4A and p21CIP1/WAF1 promoters.
- EZH2 enrichment decreased, PcG protein expression reduced, and miRNA expression targeting PcG proteins increased.
- 5-AzaC treatment resulted in decreased CpG island methylation and increased active histone marks at miRNA gene loci.
Conclusions:
- DNMTs play a critical role in regulating hUCB-MSC cellular senescence.
- DNMT inhibition impacts DNA methylation, histone modifications, and miRNA expression, collectively controlling senescence.
- Epigenetic reprogramming of hUCB-MSCs via DNMT inhibition offers insights into stem cell aging and cancer therapy.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:24Methods of Nuclear Reprogramming
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
01:14Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:29Somatic to iPS Cell Reprogramming
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...