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Related Concept Videos

Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

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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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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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Genome Copying Errors02:46

Genome Copying Errors

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DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
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Homologous Recombination02:31

Homologous Recombination

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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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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Restarting Stalled Replication Forks02:37

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Updated: Mar 6, 2026

In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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Genomic instability during reprogramming by nuclear transfer is DNA replication dependent.

Gloryn Chia1, Judith Agudo2, Nathan Treff3

  • 1Department of Pediatrics, Columbia University, New York 10032, USA.

Nature Cell Biology
|March 7, 2017
PubMed
Summary
This summary is machine-generated.

Cellular reprogramming faces barriers beyond gene expression. Genetic instability, including DNA damage and chromosome errors, arises before full reprogramming and impacts developmental success.

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Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis
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Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis
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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
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Area of Science:

  • Cellular and Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Somatic cell reprogramming to pluripotency via nuclear transfer is crucial for regenerative medicine.
  • Developmental arrest frequently occurs, often linked to incomplete transcriptional reprogramming.
  • Reprogramming involves complex changes in cell cycle and nuclear structure, not just gene expression.

Purpose of the Study:

  • To investigate cellular reprogramming events in human and mouse nuclear transfer embryos before embryonic genome activation.
  • To determine the role of cell cycle progression and nuclear structure in reprogramming barriers.
  • To identify early events contributing to developmental failure independent of transcriptional changes.

Main Methods:

  • Analysis of nuclear transfer embryos (human and mouse) prior to embryonic genome activation.
  • Assessment of chromosome segregation, DNA damage, and cell cycle progression.
  • Investigation of BRCA1's role in DNA repair during reprogramming.
  • Study of mitotic nuclear remodeling effects on DNA replication and error rates.

Main Results:

  • Genetic instability, including chromosome segregation errors and DNA damage, occurs early in reprogramming, independent of transcriptional activity.
  • These errors arise after DNA replication and are repaired by BRCA1.
  • Delayed DNA replication and increased mitotic errors are observed in the absence of proper mitotic nuclear remodeling.
  • Cell cycle progression features act as a barrier to cell-type transition.

Conclusions:

  • Cell cycle progression, independent of gene expression, presents a significant barrier to somatic cell reprogramming.
  • Early genetic instability and DNA damage are critical factors influencing reprogramming success.
  • Understanding these cell cycle-dependent barriers is essential for improving reprogramming efficiency.