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Somatic to iPS Cell Reprogramming01:29

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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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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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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.
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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Forced Transdifferentiation01:28

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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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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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Concise review: a population shift view of cellular reprogramming.

Antonio Del Sol1, Noel J Buckley

  • 1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-Belval and Life Sciences Research Unit, University of Luxembourg, Luxembourg, Luxembourg.

Stem Cells (Dayton, Ohio)
|January 23, 2014
PubMed
Summary
This summary is machine-generated.

Cellular reprogramming, while inefficient, can be improved by understanding how specific cell populations shift towards pluripotency. This population shift model explains stochastic and deterministic reprogramming, aiding regenerative medicine.

Keywords:
AttractorInduced pluripotent stem cellPluripotencyReprogramming

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Area of Science:

  • Biotechnology
  • Cell Biology
  • Regenerative Medicine

Background:

  • Cellular reprogramming is crucial for understanding disease mechanisms and developing regenerative medicine therapies.
  • Current reprogramming methods are often inefficient and incomplete, despite most somatic cells having the potential to become pluripotent.
  • Specific cell subpopulations exhibit a higher propensity for reprogramming, suggesting underlying mechanisms that are not fully understood.

Purpose of the Study:

  • To propose a population shift model for cellular reprogramming that reconciles stochastic and deterministic processes.
  • To explain why certain cell subpopulations are more readily reprogrammed.
  • To identify strategies for improving reprogramming efficiency and fidelity.

Main Methods:

  • The study proposes a theoretical model based on existing experimental observations.
  • It analyzes the dynamics of cell populations during reprogramming.
  • It considers the role of stochastic variations and epigenetic landscape modifications.

Main Results:

  • A population shift model suggests that cells closer to the pluripotent state are initially selected for reprogramming.
  • Maintaining reprogramming factor expression allows other cells to enter reprogramming pathways via stochastic variations.
  • The cell population distribution gradually shifts towards the pluripotent state over time.

Conclusions:

  • The population shift model provides a framework for understanding cellular reprogramming dynamics.
  • Understanding initial cell subpopulations and pathways can lead to improved perturbation strategies.
  • Targeting epigenetic landscapes can enhance reprogramming efficiency and fidelity for regenerative medicine applications.