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Related Concept Videos

iPS Cell Differentiation01:22

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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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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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Down syndrome iPSC model: endothelial perspective on tumor development.

Mariana Perepitchka1,2, Yekaterina Galat1,2,3,4, Igor P Beletsky3

  • 1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Oncotarget
|September 16, 2020
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Summary

Down syndrome (Trisomy 21) endothelial cells show impaired function, contributing to unique cancer profiles. These findings reveal potential therapeutic targets for leukemia and solid tumors in DS patients.

Keywords:
Down syndromeT21 genome-wide ImplicationsiPSC-derived endothelial modelmeta-analysistumor microenvironment

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Area of Science:

  • Genetics
  • Cell Biology
  • Cancer Research

Background:

  • Down syndrome (DS), caused by Trisomy 21 (T21), is associated with a distinct cancer profile, including reduced solid tumors but increased hematologic malignancies.
  • Endothelial cells are hypothesized to play a role in this unique cancer susceptibility in DS patients.

Purpose of the Study:

  • To investigate the molecular and functional differences in endothelial cells derived from DS and euploid induced pluripotent stem cells (iPSCs).
  • To determine if altered endothelial cell development and function in DS contribute to the observed cancer profile.

Main Methods:

  • Differentiation of endothelial cells from DS and euploid iPSCs.
  • Gene expression profiling using Microarray and RNA-Seq.
  • Bioinformatic analysis of gene expression data.
  • Functional assays assessing proliferation, migration, and inflammatory response (TNF-α).

Main Results:

  • Gene expression analysis revealed significant alterations in angiogenic, cytoskeletal, extracellular matrix remodeling, and inflammatory pathways in DS endothelial cells.
  • Most differentially expressed genes were not located on Chromosome 21.
  • DS endothelial cells demonstrated reduced proliferation, impaired migration, and a diminished inflammatory response to TNF-α.

Conclusions:

  • Genome-wide alterations in T21 impact endothelial cell development and function, creating a microenvironment that may hinder solid tumor growth.
  • These endothelial cell dysfunctions may also contribute to the increased risk of hematologic cancers in Down syndrome.
  • Identified genes represent potential therapeutic targets for managing cancer in DS patients.