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Related Concept Videos

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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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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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Source And Potency Of Stem Cells01:27

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Stem cells are undifferentiated cells with extensive self-renewal properties that help them maintain their population during the fetal and adult stages of life. They can specialize in all cell types of the human body. However, their differential potential may vary and can be classified into five types. Stem cells can be (1) Totipotent, (2) Pluripotent, (3) Multipotent, (4) Oligopotent, and (5) Unipotent. Each stem cell has a specific origin; the fertilized egg or zygote is a totipotent cell and...
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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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Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Na&#239;ve-like State with Improved Multilineage Differentiation Potency
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Pluripotent stem cells with low differentiation potential contain incompletely reprogrammed DNA replication.

Theodore Paniza1, Madhura Deshpande1, Ning Wang2

  • 1The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY.

The Journal of Cell Biology
|July 17, 2020
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Summary

Defects in DNA replication impact genomic stability and differentiation potential in reprogrammed pluripotent stem cells (PSCs). Analyzing DNA replication can serve as a quality control for PSCs used in research and therapy.

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Area of Science:

  • Stem cell biology
  • Genomics
  • Molecular biology

Background:

  • Reprogrammed pluripotent stem cells (PSCs) hold promise for regenerative medicine.
  • Developmental competence and genomic stability are critical for PSC safety and efficacy.
  • Existing reprogramming methods yield PSCs with variable differentiation potential.

Purpose of the Study:

  • To investigate the role of DNA replication defects in genomic instability and differentiation potential of PSCs.
  • To compare DNA replication in PSCs generated via somatic cell nuclear transfer (NT-hESCs) and induced PSCs (iPSCs).

Main Methods:

  • Utilized a single-molecule approach to visualize DNA replication dynamics in isogenic PSCs.
  • Analyzed genomic stability and DNA breaks under replicative stress.
  • Assessed DNA replication origin usage and DNA methylation patterns.

Main Results:

  • PSCs with lower differentiation potential exhibited incompletely reprogrammed DNA replication.
  • Genomic instability and DNA breaks were elevated in PSCs with impaired DNA replication.
  • Reprogramming of DNA replication did not correlate with DNA methylation status.
  • Fewer replication origins were observed in PSCs with defective DNA replication.

Conclusions:

  • Incompletely reprogrammed DNA replication contributes to genomic instability and reduced differentiation capacity in PSCs.
  • DNA replication fidelity is crucial for PSC genomic integrity and developmental potential.
  • Assessing DNA replication could be a valuable quality control measure for reprogrammed PSCs.