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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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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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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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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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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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Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological

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Somatic cell transcriptomic variation impacts induced pluripotent stem cell (iPSC) reprogramming efficiency. Ancestry influences some gene expression changes, affecting cell fate and potentially cancer survival.

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Area of Science:

  • Stem cell biology
  • Genomics
  • Personalized medicine

Background:

  • Induced pluripotent stem cells (iPSCs) are crucial for personalized disease modeling.
  • Understanding factors influencing iPSC reprogramming efficiency is vital for clinical applications.
  • Somatic cell genetic variability's impact on pluripotency is less understood than its effect on differentiation.

Purpose of the Study:

  • To investigate how transcriptomic variability in somatic cells affects reprogramming efficiency into iPSCs.
  • To identify ancestry-dependent and independent factors influencing reprogramming.
  • To explore the functional roles of genes associated with reprogramming efficiency.

Main Methods:

  • Generated and compared transcriptomic data from 72 dermal fibroblast-iPSC pairs.
  • Analyzed data considering self-reported African American and White American ancestry.
  • Utilized bioinformatics to identify differentially expressed genes and their functional associations.

Main Results:

  • Identified both ancestry-dependent and ancestry-independent transcripts associated with reprogramming efficiency.
  • Transcriptomic heterogeneity significantly impacts reprogramming.
  • Genes linked to reprogramming efficiency are involved in cancer and wound healing.
  • These genes predict 5-year breast cancer survival in an independent cohort.

Conclusions:

  • Somatic cell transcriptomic variation is a key determinant of iPSC reprogramming efficiency.
  • Candidate genes offer insights into ancestry-dependent regulation of cell fate.
  • Findings may guide improvements in reprogramming techniques for personalized medicine.