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Related Concept Videos

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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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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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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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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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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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors
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An Insight into Reprogramming Barriers to iPSC Generation.

Krishna Kumar Haridhasapavalan1, Khyati Raina1, Chandrima Dey1

  • 1Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.

Stem Cell Reviews and Reports
|November 24, 2019
PubMed
Summary

Generating induced pluripotent stem cells (iPSCs) from adult cells faces significant hurdles. Understanding these reprogramming barriers is key to developing efficient and safe methods for iPSC generation.

Keywords:
Cell reprogrammingEpigeneticsReprogramming barriers/roadblocksTranscription factorsinduced Pluripotent Stem Cells

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Area of Science:

  • Stem cell biology
  • Cellular reprogramming
  • Epigenetics

Background:

  • Induced pluripotent stem cells (iPSCs) offer revolutionary potential in regenerative medicine and disease modeling.
  • Current methods for generating iPSCs from somatic cells often suffer from low efficiency and slow kinetics.
  • Reprogramming barriers, both intrinsic and epigenetic, significantly impede the successful derivation of iPSCs.

Purpose of the Study:

  • To provide a comprehensive overview of the known barriers that inhibit the reprogramming of somatic cells into iPSCs.
  • To highlight the intrinsic and epigenetic factors that act as roadblocks during the iPSC generation process.
  • To lay the groundwork for developing improved and safer strategies for efficient iPSC reprogramming.

Main Methods:

  • Review of existing literature on iPSC generation and reprogramming barriers.
  • Analysis of intrinsic cellular factors affecting reprogramming efficiency.
  • Examination of epigenetic modifications and their role in impeding pluripotency establishment.

Main Results:

  • Identified key intrinsic barriers including non-optimal reprogramming factor stoichiometry, signaling pathway dysregulation, cellular senescence, and inhibitory transcription factors/microRNAs.
  • Highlighted the significant impact of the initial epigenetic state of somatic cells and reprogramming-induced epigenetic changes on reprogramming outcomes.
  • Underscored the complexity of overcoming these multifaceted barriers for successful iPSC derivation.

Conclusions:

  • Overcoming reprogramming barriers is crucial for advancing iPSC technology.
  • A deeper understanding of these inhibitory factors will enable the development of more efficient and safer reprogramming protocols.
  • Future strategies should focus on mitigating intrinsic cellular limitations and manipulating epigenetic landscapes to enhance iPSC generation.