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Meiosis is a carefully orchestrated set of cell divisions, the goal of which—in humans—is to produce haploid sperm or eggs, each containing half the number of chromosomes present in somatic cells elsewhere in the body. Meiosis I is the first such division, and involves several key steps, among them: condensation of replicated chromosomes in diploid cells; the pairing of homologous chromosomes and their exchange of information; and finally, the separation of homologous chromosomes by...
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Altered patterning of trisomy 21 interneuron progenitors.

Yathindar Giffin-Rao1, Jie Sheng2, Bennett Strand1

  • 1Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.

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|May 27, 2022
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Summary

Down syndrome (DS) is linked to intellectual disability and smaller brains due to impaired neurogenesis. Researchers found WNT signaling defects in DS stem cells, affecting cortical interneuron development.

Keywords:
Cortical developmentDown syndromeNeurogenesishumaniPSCsisogenicneural differentiationtrisomy 21

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Down syndrome (DS; Trisomy 21) is the most common genetic cause of intellectual disability.
  • Individuals with DS exhibit smaller brains with fewer neurons, suggesting developmental neurogenesis issues.

Purpose of the Study:

  • To investigate the developmental mechanisms underlying reduced neurogenesis in Down syndrome.
  • To identify specific cellular and molecular alterations in cortical interneuron development in DS.

Main Methods:

  • Stereological analysis of adult DS cortex.
  • Utilized Trisomy 21 (Ts21) human induced pluripotent stem cells (iPSCs) and isogenic controls.
  • Performed single-cell RNA sequencing on Ts21 progenitors.

Main Results:

  • Reduced calretinin-expressing interneurons were observed in adult DS cortex.
  • Ts21 progenitors generated fewer COUP-TFII+ progenitors with decreased proliferation.
  • Single-cell RNA sequencing revealed altered progenitor subpopulation specification and reduced WNT signaling in Ts21 cells.
  • WNT signaling activation partially rescued the COUP-TFII+ progenitor population in Ts21.

Conclusions:

  • Altered WNT signaling contributes to defective cortical interneuron development in Down syndrome.
  • These findings offer insights into the neurodevelopmental basis of intellectual disability in DS.