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Related Concept Videos

Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

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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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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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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).
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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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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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Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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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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Selecting and Isolating Colonies of Human Induced Pluripotent Stem Cells Reprogrammed from Adult Fibroblasts
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Nonstochastic reprogramming from a privileged somatic cell state.

Shangqin Guo1, Xiaoyuan Zi2, Vincent P Schulz3

  • 1Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA.

Cell
|February 4, 2014
PubMed
Summary
This summary is machine-generated.

Scientists discovered a special cell state that makes reprogramming somatic cells to pluripotency faster and non-stochastic. This breakthrough accelerates induced pluripotency by identifying and utilizing these privileged cells with ultrafast cell cycles.

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Stem Cell Research

Background:

  • Somatic cell reprogramming to induced pluripotency (iPSC) using Yamanaka factors is typically slow and inefficient.
  • The process is widely considered stochastic, meaning it occurs randomly.
  • Identifying factors that enhance reprogramming efficiency is crucial for therapeutic applications.

Purpose of the Study:

  • To identify specific somatic cell states that facilitate non-stochastic reprogramming.
  • To investigate the role of cell-cycle speed in the reprogramming process.
  • To determine if reprogramming bottlenecks can be overcome by targeting cell-cycle dynamics.

Main Methods:

  • Utilized murine hematopoietic progenitors and mouse embryonic fibroblasts (MEFs) for reprogramming experiments.
  • Employed Yamanaka factor expression for inducing pluripotency.
  • Analyzed cell-cycle duration and pluripotency acquisition rates.
  • Investigated the effect of p53 knockdown on reprogramming efficiency and cell-cycle speed.

Main Results:

  • Identified a 'privileged' somatic cell state in hematopoietic progenitors and fibroblasts exhibiting ultrafast cell cycles (approx. 8 hours).
  • Progeny of these privileged cells predominantly acquired pluripotency in a non-stochastic manner after 4-5 divisions.
  • An ultrafast cycling subpopulation in fibroblasts emerged after 6 days of factor expression, significantly enhanced by p53 knockdown.
  • This ultrafast cycling population was responsible for over 99% of the bulk reprogramming activity.

Conclusions:

  • The stochastic nature of somatic cell reprogramming can be overcome by isolating or inducing a privileged cell state.
  • Accelerated cell-cycle progression to a critical threshold is a key bottleneck in reprogramming efficiency.
  • Targeting cell-cycle dynamics offers a promising strategy to enhance induced pluripotency and its therapeutic potential.