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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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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...
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Epigenetic Regulation01:46

Epigenetic Regulation

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Epigenetic Regulation01:37

Epigenetic Regulation

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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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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Transcription01:10

Transcription

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Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Related Experiment Video

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Kinetic Measurement and Real Time Visualization of Somatic Reprogramming
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Kinetic Measurement and Real Time Visualization of Somatic Reprogramming

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Deterministic Somatic Cell Reprogramming Involves Continuous Transcriptional Changes Governed by Myc and

Asaf Zviran1, Nofar Mor2, Yoach Rais2

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 761001, Israel; New York Genome Center, New York, NY, USA.

Cell Stem Cell
|December 18, 2018
PubMed
Summary
This summary is machine-generated.

This study reveals key epigenetic changes during induced pluripotent stem cell (iPSC) reprogramming. Successful reprogramming involves distinct transcriptional modules and early DNA demethylation, driven by specific transcription factors and Myc activity.

Keywords:
Gatad2aMbd3MycNuRDdeterministic reprogrammingepigeneticsepigenomicsiPSCpluripotency

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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Generation of Myospheres From hESCs by Epigenetic Reprogramming
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Related Experiment Videos

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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Generation of Myospheres From hESCs by Epigenetic Reprogramming
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Generation of Myospheres From hESCs by Epigenetic Reprogramming

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Area of Science:

  • Epigenetics
  • Stem Cell Biology
  • Molecular Biology

Background:

  • The epigenetic landscape governing induced pluripotent stem cell (iPSC) reprogramming is not fully understood.
  • High-resolution profiling of the entire reprogramming process is needed.

Purpose of the Study:

  • To characterize the dynamic epigenetic changes during mouse fibroblast to iPSC conversion.
  • To identify key molecular players and transcriptional modules driving successful reprogramming.

Main Methods:

  • Utilized Gatad2a-Mbd3/NuRD-depleted reprogramming systems for high efficiency.
  • Performed unbiased, high-resolution profiling of gene expression, chromatin, DNA accessibility, and methylation dynamics.

Main Results:

  • Identified two synergistic transcriptional modules: one for cell identity (pluripotency) and one for biosynthesis.
  • Pluripotency module dynamics involve epigenetic modifications and binding of Oct4, Sox2, and Klf4 (not Myc).
  • Early DNA demethylation at enhancers predicts successful reprogramming; Myc drives biosynthesis and tRNA modifications.

Conclusions:

  • Successful iPSC reprogramming is a rapid, deterministic process driven by intertwined epigenetic regulation and Myc activity.
  • Epigenetic modifications and Myc-driven biosynthesis are essential for achieving naive pluripotency.