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Related Concept Videos

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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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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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 Cells01:13

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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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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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Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming.

Lei Yang1, Xuefei Liu1, Lishuang Song1,2

  • 1State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), Inner Mongolia University, Hohhot, China.

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|July 28, 2020
PubMed
Summary

Researchers identified key factors, Dux, Dppa2, and Dppa4, that enhance zygotic genome activation (ZGA) in cloned embryos. Transient Dux overexpression significantly improved cloning efficiency and embryo development, advancing somatic cell reprogramming understanding.

Keywords:
Dppa2/4DuxSCNTchemically induced pluripotent stem cellszygotic genome activation

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Area of Science:

  • Developmental Biology
  • Reproductive Biology
  • Genetics

Background:

  • Somatic cell nuclear transfer (SCNT) is a cloning technique with low efficiency.
  • Zygotic genome activation (ZGA) is crucial for reprogramming somatic cells in SCNT but remains poorly understood.
  • Identifying factors that promote ZGA is essential for improving SCNT efficiency.

Purpose of the Study:

  • To identify novel factors that enhance ZGA in SCNT-mediated reprogramming.
  • To investigate the role of identified factors in improving SCNT efficiency and subsequent embryonic development.
  • To explore strategies for enhancing the developmental potential of SCNT-derived embryos.

Main Methods:

  • Performed siRNA-repressor and mRNA-inducer screenings to identify ZGA-enhancing factors.
  • Established an inducible Dux transgenic mouse model for transient Dux overexpression.
  • Utilized transcriptome profiling to analyze Dux-treated SCNT embryos.
  • Investigated the combined effect of Dux overexpression and DNA methyltransferase (Dnmt) inactivation.

Main Results:

  • Identified Dux, Dppa2, and Dppa4 as key factors enhancing ZGA in SCNT.
  • Transient Dux overexpression significantly improved SCNT efficiency and chemically induced pluripotent stem cell reprogramming.
  • Dux-treated SCNT embryos exhibited transcriptome profiles similar to fertilized embryos.
  • Combined Dux overexpression and Dnmt inactivation promoted full embryonic development of SCNT-derived animals.

Conclusions:

  • Dux, Dppa2, and Dppa4 are critical regulators of ZGA in SCNT.
  • Transient Dux overexpression is a promising strategy to enhance SCNT efficiency and reprogramming.
  • Targeting ZGA regulators, like Dux, offers a pathway to improve the developmental capacity of cloned embryos and advance regenerative medicine.