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Related Concept Videos

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 for this...
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 injury repair.
Abnormal Proliferation02:23

Abnormal 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...
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...
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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

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Kinetic Measurement and Real Time Visualization of Somatic Reprogramming
08:56

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Published on: July 30, 2016

Stress-mediated p38 activation promotes somatic cell reprogramming.

Xinxiu Xu1, Quan Wang, Yuan Long

  • 1Laboratory of Receptor-based Bio-medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

Cell Research
|October 10, 2012
PubMed
Summary
This summary is machine-generated.

Environmental stress, like hyperosmosis, significantly enhances induced pluripotent stem cell (iPSC) generation. This occurs through p38 activation, which modulates epigenetic factors and boosts pluripotency gene expression.

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Area of Science:

  • Cellular biology
  • Epigenetics
  • Stem cell research

Background:

  • Environmental stress drives adaptation and evolution through gene expression regulation.
  • Cellular adaptation involves chromatin structure, transcription, mRNA stability, and translation.
  • Epigenetic changes are crucial for reprogramming somatic cells into induced pluripotent stem cells (iPSCs).

Purpose of the Study:

  • To investigate the role of environmental stress, specifically hyperosmosis, in facilitating iPSC generation.
  • To elucidate the molecular mechanisms, including signaling pathways and epigenetic modifications, underlying stress-enhanced reprogramming.

Main Methods:

  • Utilized hyperosmotic stress during the reprogramming process.
  • Investigated the role of p38 mitogen-activated protein kinase (MAPK) pathway activation using constitutively active and dominant-negative forms, as well as inhibitors.
  • Assessed global DNA methylation levels and pluripotency gene expression.

Main Results:

  • Hyperosmosis significantly enhanced iPSC generation, even with fewer reprogramming factors (two or one).
  • p38 pathway activation was critical, with its activation mimicking hyperosmosis's effect and inhibition blocking it.
  • Stress-mediated p38 activation reduced global DNA methylation and increased pluripotency gene expression.

Conclusions:

  • Environmental stress, such as hyperosmosis, can be leveraged to improve the efficiency of iPSC generation.
  • The p38 signaling pathway and epigenetic modulation, specifically DNA demethylation, are key mediators of stress-induced reprogramming.
  • This study reveals a novel mechanism by which environmental cues influence cellular fate and epigenetic states.