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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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Induced Pluripotent Stem Cells01:13

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Induced Pluripotent Stem Cells01:13

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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Induced Pluripotent Stem Cells01:06

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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
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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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Chromatin Modification in iPS Cells01:32

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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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Cell signalling pathways underlying induced pluripotent stem cell reprogramming.

Kate Hawkins1, Shona Joy1, Tristan McKay1

  • 1Kate Hawkins, Shona Joy, Tristan McKay, Molecular Cell Sciences, St George's University of London, London SW17 0RE, United Kingdom.

World Journal of Stem Cells
|November 27, 2014
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Summary

Generating induced pluripotent stem (iPS) cells is inefficient due to poor understanding of reprogramming. Research into cell signaling pathways has revealed a 3-stage model to improve iPS cell generation efficiency and safety.

Keywords:
Cell signallingEmbryonic stemInduced pluripotent stemPluripotencyReprogramming

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Area of Science:

  • Stem cell biology
  • Cellular reprogramming
  • Regenerative medicine

Background:

  • Induced pluripotent stem (iPS) cells are valuable for research and regenerative medicine but reprogramming remains inefficient.
  • Incomplete mechanistic understanding of reprogramming hinders safety, reproducibility, and efficiency.
  • Investigating cell signaling pathways is key to improving iPS cell generation.

Purpose of the Study:

  • To elucidate the mechanistic understanding of the iPS cell reprogramming process.
  • To identify new mechanisms for improving the safety, reproducibility, and efficiency of iPS cell generation.
  • To present a unified model of reprogramming.

Main Methods:

  • Interrogation of cell signaling pathways including LIF/STAT3, BMP, PI3K, FGF2, Wnt, TGFβ, and MAPK.
  • Analysis of the 3 stages of reprogramming: initiation, maturation, and stabilization.
  • Characterization of phenotypic changes, proliferation, and metabolic shifts during reprogramming.

Main Results:

  • A unified 3-stage model of reprogramming (initiation, maturation, stabilization) has been established.
  • Initiation involves a mesenchymal-to-epithelial transition, increased proliferation, and a metabolic switch.
  • Maturation is a bottleneck; successful cells activate endogenous pluripotency genes (Oct4, Sox2, Nanog) for transgene independence.

Conclusions:

  • Understanding cell signaling pathways provides a framework for improving iPS cell generation.
  • The 3-stage model offers insights into the major challenges and critical checkpoints in reprogramming.
  • Further development of interrogation tools will enhance understanding of this biological phenomenon.