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Telomeres and Telomerase02:41

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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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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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Telomerase reverse transcriptase has an extratelomeric function in somatic cell reprogramming.

Taisuke Kinoshita1, Go Nagamatsu2, Shigeru Saito3

  • 1From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, 160-8582.

The Journal of Biological Chemistry
|April 16, 2014
PubMed
Summary
This summary is machine-generated.

Telomerase reverse transcriptase (TERT) aids somatic cell reprogramming but is not essential. TERT plays an extratelomeric role, crucial for genome stability in induced pluripotent stem cells.

Keywords:
BioinformaticsInduced Pluripotent Stem (iPS) CellMicroarrayReprogrammingTelomeres

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Area of Science:

  • Stem Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Telomerase reverse transcriptase (TERT) reactivation and telomere elongation are key events in induced pluripotent stem (iPS) cell generation.
  • The specific role of TERT in the reprogramming process remains largely undefined.

Purpose of the Study:

  • To investigate the function of TERT during somatic cell reprogramming.
  • To differentiate between telomere-dependent and extratelomeric roles of TERT in this process.

Main Methods:

  • Reprogramming of TERT-knockout (TERT-KO) mouse tail-tip fibroblasts (TTFs).
  • Analysis of reprogramming efficiency, gene expression profiles, and teratoma formation.
  • Assessment of genome stability and chromosome integrity in iPS cells.
  • Rescue experiments using an enzymatically inactive TERT mutant.

Main Results:

  • TERT-KO iPS cells were generated, but with significantly lower efficiency than wild-type (WT) cells.
  • TERT-KO iPS cells exhibited transient growth defects and accumulated chromosome fusions over time.
  • An inactive TERT mutant rescued reprogramming efficiency, confirming an extratelomeric function.

Conclusions:

  • TERT plays a dispensable extratelomeric role in somatic cell reprogramming.
  • TERT is essential for maintaining genome stability and structure in iPS cells.
  • TERT's extratelomeric function is critical for robust iPS cell generation and maintenance.