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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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Methods of Nuclear Reprogramming01:24

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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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Maintenance of the ES Cell State01:14

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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...
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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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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS 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.
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...
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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.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Related Experiment Video

Updated: Apr 7, 2026

Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance.

Duygu Ozmadenci1, Olivier Féraud2, Suzy Markossian3

  • 1Apoptosis, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.

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Netrin-1 and its receptor DCC modulate induced pluripotent stem cell generation. Correcting their balance reduces apoptosis and enhances reprogramming efficiency for regenerative medicine applications.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Regenerative Medicine

Background:

  • Induced pluripotent stem (iPS) cell generation is crucial for regenerative medicine.
  • While transcription factors are known reprogramming drivers, soluble factors remain underexplored.

Purpose of the Study:

  • To identify novel soluble molecules that modulate the efficiency of somatic cell reprogramming into iPS cells.
  • To investigate the role of Netrin-1 and its receptor DCC in the reprogramming process.

Main Methods:

  • Analysis of Netrin-1 expression during somatic cell reprogramming.
  • Investigating the mechanism of Netrin-1 regulation by the NuRD complex.
  • Assessing the impact of Netrin-1/DCC pathway modulation on apoptosis and reprogramming efficiency.
  • Evaluating the effect of recombinant Netrin-1 on iPS cell generation in mouse and human cells.

Main Results:

  • Netrin-1 expression is transiently repressed during reprogramming by the Mbd3/Mta1/Chd4 NuRD complex.
  • Netrin-1 imbalance, mediated by DCC, induces p53-independent apoptosis.
  • Restoring Netrin-1/DCC equilibrium reduces apoptosis and improves reprogramming efficiency.
  • Netrin-1 also protects embryonic stem cells from apoptosis via UNC5b.
  • Recombinant Netrin-1 treatment enhances mouse and human iPS cell generation.

Conclusions:

  • Netrin-1 and DCC are key modulators of reprogramming efficiency by controlling apoptosis.
  • Targeting the Netrin-1/DCC pathway offers a novel strategy to improve iPS cell generation for regenerative medicine.
  • This study elucidates a new role for Netrin-1 in cell survival and reprogramming.