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Related Concept Videos

Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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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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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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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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An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
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DNA methylation dynamics in human induced pluripotent stem cells.

Koichiro Nishino1,2, Akihiro Umezawa3

  • 1Laboratory of Veterinary Biochemistry and Molecular Biology, Graduate School of Medicine and Veterinary Medicine, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen-Kibanadai-Nishi, Miyazaki, 889-2192, Japan. aknishino@cc.miyazaki-u.ac.jp.

Human Cell
|April 17, 2016
PubMed
Summary

Human induced pluripotent stem cells (hiPSCs) show similar epigenetic patterns to embryonic stem cells (hESCs). Aberrant DNA methylation differences decrease with passaging, suggesting an index for evaluating hiPSCs in regenerative medicine.

Keywords:
DNA methylationEpigeneticsHuman induced pluripotent stem cellsReprogramming

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Regenerative medicine

Background:

  • Human induced pluripotent stem cells (hiPSCs) are crucial for regenerative medicine.
  • Understanding reprogramming mechanisms, particularly epigenetic modifications, is key to hiPSC generation.
  • Genome-wide epigenetic changes are critical events during somatic cell transformation into hiPSCs.

Purpose of the Study:

  • To elucidate reprogramming processes by analyzing epigenetic changes in hiPSCs.
  • To compare DNA methylation profiles of hiPSCs from various tissues with human embryonic stem cells (hESCs).
  • To identify potential epigenetic markers for evaluating hiPSC quality for therapeutic applications.

Main Methods:

  • Generation of numerous hiPSCs from diverse human tissues.
  • Whole-genome DNA methylation profiling of established hiPSCs.
  • Comparative analysis of epigenetic patterns between hiPSCs and hESCs across different passages.

Main Results:

  • Epigenetic patterns of hiPSCs were largely similar across different tissue origins and comparable to hESCs.
  • Initial hiPSC passages showed epigenetic differences from hESCs due to aberrant hypermethylation.
  • Continuous passaging of hiPSCs reduced these epigenetic discrepancies with hESCs.

Conclusions:

  • DNA methylation profiles of hiPSCs resemble those of hESCs, indicating successful reprogramming.
  • Aberrant DNA methylation patterns in early hiPSC passages diminish with passaging.
  • The number of aberrant DNA methylation regions can serve as an epigenetic index for assessing hiPSCs for therapeutic use.