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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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 for this...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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 injury repair.
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
Forced Transdifferentiation01:28

Forced Transdifferentiation

Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

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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Reprogramming Pancreatic Ductal Adenocarcinoma to Pluripotency
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Epigenetic reprogramming of mesenchymal stem cells.

Yu-Wei Leu1, Tim H-M Huang, Shu-Huei Hsiao

  • 1Department of Life Science, National Chung Cheng University, Chia-Yi 621, Taiwan. bioywl@ccu.edu.tw

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Targeted DNA methylation of specific genes in mesenchymal stem cells (MSCs) can control their differentiation and potential for tumor formation. This technique offers new possibilities for MSC applications in regenerative medicine.

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Cancer research

Background:

  • Mesenchymal stem cells (MSCs) are multipotent cells with therapeutic potential but carry a risk of tumorigenesis.
  • Epigenomic modifications, particularly DNA methylation, are implicated in MSC differentiation and cancer development.
  • The precise role of DNA methylation in MSC tumorigenesis and differentiation control remains under investigation.

Purpose of the Study:

  • To investigate the impact of targeted DNA methylation on mesenchymal stem cell (MSC) fate determination.
  • To explore the potential of manipulating epigenomic changes for controlling MSC differentiation and tumorigenesis.
  • To establish a novel method for precise epigenetic modification in MSCs.

Main Methods:

  • Application of a targeted DNA methylation technique to specific genes in MSCs.
  • Methylation of the Polycomb group protein-governed gene, Trip10, to influence cell fate.
  • Targeted methylation of tumor suppressor genes, HIC1 and RassF1A, to assess transformation potential.

Main Results:

  • Targeted methylation of Trip10 accelerated the cell fate determination of MSCs.
  • Methylation of HIC1 and RassF1A transformed MSCs into cells resembling tumor stem cells.
  • Demonstrated a direct link between targeted DNA methylation and altered MSC behavior.

Conclusions:

  • Targeted DNA methylation is a viable strategy to control MSC differentiation pathways.
  • This method provides a means to induce or inhibit tumorigenesis in MSCs.
  • The developed technique offers enhanced control over MSCs for future therapeutic and research applications.