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Related Concept Videos

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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Chromatin Modification in iPS Cells01:32

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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.
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...
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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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Introduction to Nuclear Reprogramming01:14

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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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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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Induced Pluripotent Stem Cells01:06

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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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Expression level of pluripotent genes in incomplete reprogramming.

Xing Zhao1, Qi Li2, Wei-Min Jiang2

  • 1First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China.

Asian Pacific Journal of Tropical Medicine
|August 24, 2014
PubMed
Summary

Incomplete reprogramming may stem from incorrect expression of key genes like Oct4, Sox2, Klf4, and C-Myc. Achieving successful induced pluripotent stem cells (iPSCs) likely requires a precise balance of these factors.

Keywords:
Human foreskin fibroblastIncomplete reprogrammingInduced pluripotent stem cellReprogramming

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular biology

Background:

  • Induced pluripotent stem cells (iPSCs) hold promise for regenerative medicine.
  • Understanding the reprogramming process is crucial for generating functional iPSCs.
  • Incomplete reprogramming can lead to unstable cell lines.

Purpose of the Study:

  • To compare pluripotent gene expression in partially reprogrammed colonies versus iPSCs.
  • To investigate the link between gene expression and reprogramming efficiency.

Main Methods:

  • Human foreskin fibroblasts (HFFs) were transduced with Oct4, Sox2, Klf4, and C-Myc.
  • Colonies were analyzed for morphology, alkaline phosphatase (AP) staining, immuno-fluorescence, and quantitative PCR (Q-PCR).

Main Results:

  • Partially reprogrammed colonies showed some stem cell characteristics but were unstable.
  • These colonies had weak AP staining and only expressed Oct4 protein.
  • Q-PCR revealed inappropriate expression levels of exogenous factors and low expression of endogenous pluripotency genes.

Conclusions:

  • Inappropriate expression (too high or too low) of exogenous pluripotent genes may cause incomplete reprogramming.
  • Successful reprogramming to iPSCs may depend on a specific stoichiometric balance of Oct4, Sox2, Klf4, and C-Myc.