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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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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 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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Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
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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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Non-nuclear Inheritance01:29

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Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
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Mitochondrial DNA Dynamics in Reprogramming to Pluripotency.

Alexander J Sercel1, Natasha M Carlson2, Alexander N Patananan3

  • 1Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA 90095.

Trends in Cell Biology
|January 10, 2021
PubMed
Summary
This summary is machine-generated.

Mitochondrial DNA (mtDNA) heteroplasmy shifts in induced pluripotent stem cells (iPSCs) can be manipulated. Understanding these changes impacts stem cell therapies and disease modeling.

Keywords:
heteroplasmyinduced pluripotent stem cellmitochondrial DNApluripotencyreprogramming

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Area of Science:

  • Cell Biology
  • Genetics
  • Stem Cell Research

Background:

  • Mitochondria are vital organelles in mammalian cells, essential for energy production and cellular functions.
  • Mitochondrial DNA (mtDNA) exists in multiple copies and can exhibit heteroplasmy, where different genotypes coexist due to mutations.

Purpose of the Study:

  • To investigate mechanisms maintaining or altering mtDNA heteroplasmy during cellular reprogramming into induced pluripotent stem cells (iPSCs).
  • To explore how manipulating mtDNA heteroplasmy can influence stem and differentiated cell performance.
  • To enhance the development of iPSC-based disease models and cell therapies.

Main Methods:

  • Analysis of mtDNA heteroplasmy dynamics in iPSCs generated through cellular reprogramming.
  • Exploration of methods to intentionally alter mtDNA heteroplasmy levels.

Main Results:

  • Identified potential mechanisms governing the maintenance and shifts of mtDNA heteroplasmy in iPSCs.
  • Demonstrated that mtDNA heteroplasmy can be manipulated to affect cell function.

Conclusions:

  • Understanding mtDNA heteroplasmy dynamics in iPSCs is crucial for their therapeutic applications.
  • Targeted alteration of mtDNA heteroplasmy offers a novel strategy for improving iPSC-based disease modeling and regenerative medicine.