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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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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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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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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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Pramef12 enhances reprogramming into naïve iPS cells.

Daiki Haraguchi1, Toshinobu Nakamura1,2,3

  • 1Gaduate School of Bio-Science, Japan.

Biochemistry and Biophysics Reports
|May 20, 2022
PubMed
Summary

Preferentially expressed antigen of melanoma family member 12 (Pramef12), found in oocytes, boosts induced pluripotent stem (iPS) cell generation. Pramef12 enhances reprogramming efficiency by activating the Wnt/β-catenin pathway.

Keywords:
Pramef12ReprogrammingWnt/β-catenin pathwayiPS cells

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Developmental biology

Background:

  • Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells using defined transcription factors (OKSM).
  • Oocyte-derived factors may enhance reprogramming efficiency, as suggested by somatic cell nuclear transfer studies.
  • Preferentially expressed antigen of melanoma family member 12 (Pramef12) is highly expressed in oocytes.

Purpose of the Study:

  • To investigate the role of Pramef12 in enhancing induced pluripotent stem cell generation.
  • To elucidate the molecular mechanisms by which Pramef12 influences reprogramming.

Main Methods:

  • Overexpression of Pramef12 in mouse fibroblasts during OKSM-induced reprogramming.
  • Analysis of pluripotency-associated gene expression (including Gtl2 in the Dlk1-Dio3 imprinted region).
  • Assessment of metabolic gene expression (glycolysis and oxidative phosphorylation).
  • Evaluation of mesenchymal-to-epithelial transition (MET).
  • Measurement of β-catenin activation.

Main Results:

  • Overexpression of Pramef12 significantly enhanced the efficiency of iPS cell derivation.
  • Pramef12 promoted the expression of naïve pluripotency genes, Gtl2, glycolysis-related genes, and oxidative phosphorylation-related genes.
  • Pramef12 facilitated mesenchymal-to-epithelial transition during iPS cell generation.
  • Pramef12 strongly activated β-catenin signaling.

Conclusions:

  • Pramef12 enhances OKSM-induced reprogramming of somatic cells into iPS cells.
  • Pramef12-mediated enhancement of reprogramming is associated with activation of the Wnt/β-catenin pathway.