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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...
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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...
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Methods of Nuclear Reprogramming01:24

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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...
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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Published on: June 7, 2019

Epigenetic reprogramming as a key contributor to melanocyte malignant transformation.

Fernanda Molognoni1, Adriana T Cruz, Fabiana M Meliso

  • 1Pharmacology Department, Universidade Federal de São Paulo, São Paulo, Brazil.

Epigenetics
|February 24, 2011
PubMed
Summary

Microenvironmental stress triggers epigenetic reprogramming in melanocytes, driving melanoma progression. These epigenetic changes are crucial for malignant transformation and maintaining the cancerous phenotype.

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Area of Science:

  • Cancer Biology
  • Epigenetics
  • Melanoma Research

Background:

  • Melanoma progression involves gene expression deregulation via unknown epigenetic mechanisms.
  • A novel mouse model was developed to study melanocyte malignant transformation induced by microenvironmental changes.

Purpose of the Study:

  • To identify factors contributing to epigenetic modifications during early and late stages of malignant transformation.
  • To understand the role of epigenetic alterations in melanoma development and progression.

Main Methods:

  • Development of melanocyte cell lines (melan-a, 4C, 4C11-, 4C11+) through sequential anchorage blockade.
  • Analysis of global and gene-specific DNA methylation and histone modifications.
  • Treatment with epigenetic modifiers (5-Aza-2'-deoxycytidine, Trichostatin A) to assess impact on transformation and tumor growth.

Main Results:

  • Early epigenetic alterations, including DNA methylation and histone marks, were observed in the 4C cell line.
  • Distinct histone modifications correlated with gene and microRNA expression changes across cell lines.
  • Inhibition of epigenetic changes prevented melanocyte transformation and reduced tumor growth in established melanoma cell lines.

Conclusions:

  • Sustained microenvironmental stress induces epigenetic reprogramming in melanocytes.
  • Epigenetic alterations are critical for both the initiation and maintenance of the malignant melanoma phenotype.
  • Epigenetic reprogramming provides a potential therapeutic target for melanoma treatment.