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Related Concept Videos

Introduction to Nuclear Reprogramming01:14

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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...
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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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Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
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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.
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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...
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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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Updated: Jun 26, 2025

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Oct4 redox sensitivity potentiates reprogramming and differentiation.

Zuolian Shen1,2, Yifan Wu1,2, Asit Manna1,2

  • 1Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.

Genes & Development
|May 8, 2024
PubMed
Summary
This summary is machine-generated.

The transcription factor Oct4, crucial for pluripotency, is regulated by a redox-sensitive DNA binding domain. This discovery reveals a novel mechanism controlling cellular reprogramming and differentiation.

Keywords:
Oct1 (Pou2f1)Oct4 (Pou5f1)induced pluripotent stem cells (iPSCs)oxidative stressubiquitylation

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Oct4 (Pou5f1) is a key transcription factor regulating pluripotency.
  • Oct4 is widely used to induce pluripotency in somatic cells.
  • Understanding Oct4's regulatory mechanisms is vital for regenerative medicine.

Purpose of the Study:

  • To investigate the reprogramming ability of Oct4.
  • To identify key determinants of Oct4's function in reprogramming and differentiation.
  • To elucidate the role of redox sensitivity in Oct4 activity.

Main Methods:

  • Domain swapping and mutagenesis of Oct4.
  • Analysis of Oct4 DNA binding activity under oxidative stress.
  • Generation and characterization of Pou5f1 mutant mice and embryonic stem cells (ESCs).

Main Results:

  • A redox-sensitive DNA binding domain, involving cysteine residue Cys48, was identified as critical for Oct4 function.
  • Oct4 Cys48 regulates DNA binding via oxidative inhibition and promotes ubiquitylation.
  • Pou5f1 mutations lead to aberrant differentiation, poor teratoma formation, and developmental defects in mice.

Conclusions:

  • A novel Oct4 redox mechanism controls both entry into and exit from pluripotency.
  • Cys48 is a key determinant of Oct4's role in cellular reprogramming and differentiation.
  • This finding has implications for understanding stem cell biology and therapeutic applications.