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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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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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Inheritance of Chromatin Structures03:17

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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.

Xiaojian Shao, Cuiyun Zhang, Ming-An Sun

  • 1Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. luxm@big.ac.cn.

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Human induced pluripotent stem cells (iPSCs) show decreased DNA methylation variation compared to differentiated cells, particularly in repetitive elements. This study offers insights into methylation dynamics during cell reprogramming and differentiation.

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Area of Science:

  • Epigenetics
  • Stem Cell Biology
  • Genomics

Background:

  • Human induced pluripotent stem cells (iPSCs) are crucial for research, disease modeling, and drug screening.
  • Epigenetic instability in iPSCs, including aberrant DNA methylation, can lead to cancer.
  • Limited comparative studies exist on epigenetic variation between iPSCs and differentiated cells.

Purpose of the Study:

  • To develop an analytical method for deciphering DNA methylation heterogeneity in mixed cell populations.
  • To quantitatively assess DNA methylation variation in adipose-derived stem cells (ADS), differentiated ADS-adipocytes, and reprogrammed ADS-iPSCs.
  • To understand methylation dynamics during stem cell differentiation and reprogramming.

Main Methods:

  • Development of a novel analytical procedure for DNA methylation heterogeneity analysis.
  • Quantitative assessment of DNA methylation variation across the methylomes of ADS, ADS-adipocytes, and ADS-iPSCs.
  • Analysis of methylation variation in specific genomic regions (promoters, 5'UTR, Satellite) and repetitive elements.

Main Results:

  • DNA methylation variation differs across genomic regions; promoters and 5'UTRs show low variation, while Satellite regions exhibit high variation.
  • ADS-iPSCs display globally decreased DNA methylation variation compared to differentiated cells, especially in repetitive elements.
  • Promoter methylation variation decreases during differentiation but increases during reprogramming, negatively correlating with gene expression.

Conclusions:

  • The study presents a method to detect cell-subset specific methylation genes within mixed cell populations.
  • Provides a deeper understanding of DNA methylation dynamics during stem cell differentiation and reprogramming processes.