Related Experiment Video

Updated: Jul 23, 2025

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells
08:01

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells

Published on: August 29, 2020

2.3K

Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific

Xiuling Fu1, Qiang Zhuang1, Isaac A Babarinde1

  • 1Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.

Cell Death Discovery
|July 14, 2023
PubMed

Insights

Transformed cells resist reprogramming due to epigenetic barriers. This study identified diverse barriers and showed MEK inhibition can overcome one, enabling reprogramming of some cancer cells.

Area of Science:

  • Cell biology
  • Epigenetics
  • Cancer research

Background:

  • Somatic cell reprogramming and oncogenic transformation share similarities.
  • Transformed cells are generally resistant to reprogramming.
  • The nature of epigenetic barriers blocking reprogramming in transformed cells is not well understood.

Purpose of the Study:

  • To investigate the epigenetic barriers preventing reprogramming in oncogenically transformed cells.
  • To identify factors and stages contributing to reprogramming resistance.
  • To explore strategies for overcoming reprogramming resistance in transformed cells.

Main Methods:

  • Generated a panel of oncogenically transformed mouse embryonic fibroblasts (MEFs).
  • Transfected transformed MEFs with reprogramming factors (Oct4/Sox2/Klf4/Myc).
  • Compared reprogramming-capable and incapable transformed lines; utilized MEK inhibition.

Main Results:

  • Identified transformed cell lines capable of reprogramming upon Oct4/Sox2/Klf4/Myc transfection.
  • Discovered multiple reprogramming failure stages in resistant transformed lines.
  • Demonstrated MEK inhibition overcomes a reprogramming barrier by suppressing a hyperacetylated epigenetic state.

Conclusions:

  • Diverse epigenetic barriers underlie the resistance of transformed cells to reprogramming.
  • Understanding these barriers is crucial for advancing reprogramming technologies.
  • Targeting specific epigenetic states, like those modulated by MEK inhibition, can restore reprogramming capacity.

More Related Videos

Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors08:14

Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors

Published on: October 28, 2014

12.9K
RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells11:38

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells

Published on: November 26, 2018

10.5K

Related Concept Videos

Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Somatic to iPS Cell Reprogramming01:29

Somatic 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...
2.2K
Methods of Nuclear Reprogramming01:24

Methods 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...
1.8K
Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
2.0K
Maintenance of the ES Cell State01:14

Maintenance 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...
2.2K
Epigenetic Regulation01:37

Epigenetic 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...
3.1K