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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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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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Forced Transdifferentiation01:28

Forced Transdifferentiation

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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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Induced Pluripotent Stem Cell Generation from Blood Cells Using Sendai Virus and Centrifugation
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Direct cell reprogramming is a stochastic process amenable to acceleration.

Jacob Hanna1, Krishanu Saha, Bernardo Pando

  • 1The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. Hanna@wi.mit.edu

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|November 10, 2009
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Summary
This summary is machine-generated.

Reprogramming somatic cells to induced pluripotent stem (iPS) cells is a continuous process. Cell division rate and Nanog influence reprogramming speed, highlighting cell divisions as key to epigenetic changes.

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular biology

Background:

  • Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells is typically achieved by overexpressing Oct4, Sox2, Klf4, and c-Myc.
  • However, only a small fraction of somatic cells successfully undergo reprogramming.

Purpose of the Study:

  • To investigate the kinetics and mechanisms underlying the reprogramming process.
  • To identify factors that influence the efficiency and speed of induced pluripotency induction.

Main Methods:

  • Overexpression of reprogramming factors (Oct4, Sox2, Klf4, c-Myc) in mouse somatic cells.
  • Inhibition of the p53/p21 pathway.
  • Overexpression of Lin28 and Nanog.
  • Quantitative analysis of reprogramming kinetics and cell proliferation rates.

Main Results:

  • Reprogramming is a continuous stochastic process, with most cells eventually becoming iPS cells upon sustained expression and growth.
  • Inhibition of p53/p21 or Lin28 overexpression accelerated iPS cell formation proportionally to increased cell division rates.
  • Nanog overexpression accelerated reprogramming independently of cell division rate.
  • Distinct cell-division-rate-dependent and -independent modes of reprogramming acceleration were identified.

Conclusions:

  • The number of cell divisions is a critical parameter driving epigenetic reprogramming to pluripotency.
  • Both cell proliferation rates and specific factors like Nanog play significant roles in modulating reprogramming kinetics.