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PreprintCited by 38Neurogenesis and neuroplasticity mechanismsDown syndrome and intellectual disability researchPluripotent Stem Cells Research

The DOI matches its Crossref record, with a small difference in title or year; 1 of the 1 references it cites were found in a registry or an index.

Altered patterning of trisomy 21 interneuron progenitors

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Giffin-Rao, Yathindar, Sheng, Jie, Strand, Bennett, Xu, Ke, Huang, Leslie, Medo, Margaret, Risgaard, Kirstin A., Dantinne, Samuel, Mohan, Sruti, Keshan, Aratrika, Daley, Roger A., Levesque, Bradley, Amundson, Lindsey, Reese, Rebecca, Sousa, André M.M., Tao, Yunlong, Wang, Daifeng, Zhang, Su-Chun, Bhattacharyya, Anita·2020·Stem Cell Reports
DOI 10.1101/2020.02.18.951756PMC PMC9214050

Preprint — published as 10.1016/j.stemcr.2022.05.001 · Paper page

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Abstract

SUMMARY: Individuals with Down syndrome (DS, Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single cell RNA-sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.

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  • Another study analyzing a similar age group and area found no difference in parvalbumin or calretinin positive interneurons in Down syndrome.

    “However, another study analyzing a similar age group and area found no difference in parvalbumin or calretinin positive interneurons (Giffin-Rao et al., 2020).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Giffin-Rao et al., 2020

    In “Fewer neurons in DS cortex” (page unavailable), the paper reports no difference in parvalbumin-positive cell density in age-matched superior temporal gyrus samples (ages 15–35). It does not make the same unqualified finding for calretinin-positive cells: it reports a lower measured density in Down syndrome that may indicate a reduction, although the comparison was not statistically significant (p=0.11). (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Hypocellularity persists with fewer total neurons being identified in the superior temporal gyrus in adolescents and adults with Down syndrome (15-35 years).

    “The hypocellularity persists with fewer total neurons being identified in the superior temporal gyrus in adolescents and adults with DS (15–35 years) (Ross et al., 1984; Giffin-Rao et al., 2020).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Giffin-Rao et al., 2020

  • Trisomic iPSC-derived NPCs exhibit more ventral and fewer caudal characteristics compared to euploid controls.

    “The trisomic NPCs exhibited more ventral and fewer caudal characteristics compared to their euploid controls exposed to the same patterning agents (Giffin-Rao et al., 2020).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Giffin-Rao et al., 2020

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Metadata

Authors
Giffin-Rao, Y., Sheng, J., Strand, B., Xu, K., Huang, L., Medo, M., Risgaard, K. A., Dantinne, S., Mohan, S., Keshan, A., Daley, R. A., Levesque, B., Amundson, L., Reese, R., Sousa, A. M. M., Tao, Y., Wang, D., Zhang, S.-C., & Bhattacharyya, A.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Bhattacharyya, Anita
ORCID
Venue
Stem Cell Reports
Publisher
openRxiv
Published
2020-02-19
Volume
17
Issue
6
Pages
1366-1379
ISSN
2213-6711 (ISSN-L)
DOI
10.1101/2020.02.18.951756
PMC
PMC9214050
OpenAlex
W4281558139
Cited by
38
References
1
Citations by year
2026: 9 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 2
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Wisconsin Alumni Research Foundation
  • University of Wisconsin-Madison
  • Waisman Center (HD090256, U54 HD090256)
  • National Institutes of Health (HD090256)
  • College of Engineering, University of Wisconsin-Madison
  • National Institute of Neurological Disorders and Stroke (R21NS105339, R01NS096282)
  • National Institute of Child Health and Human Development (HD090256)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD090256, R03HD083538, R01HD106197)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
Down syndrome, COUP-TFII, Wnt signaling, calretinin, neurogenesis, intellectual disability, iPSC-derived neurons, progenitor cell proliferation
MeSH terms
Adult, Down Syndrome, Humans, Interneurons, Neurons, Trisomy, Neurogenesis, Induced Pluripotent Stem Cells

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