ArticleFrontiers in molecular neuroscience2023
Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of Down syndrome.
Article in Frontiers in molecular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- Short-lived Niemann-Pick type C mice with accelerated brain aging as a novel model for Alzheimer's disease research.Neural regeneration research · 2026Article
- Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions.American journal of human genetics · 2025Article
- Unveiling distinctions between mesenchymal stromal cells and stem cells by single-cell transcriptomic analysis.Heliyon · 2025Article
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- The mTOR Pathway: A Common Link Between Alzheimer's Disease and Down Syndrome.Journal of clinical medicine · 2024Review
- Beyond Quiescent and Active: Intermediate Microglial Transcriptomic States in a Mouse Model of Down Syndrome.International journal of molecular sciences · 2024Article
- Transcriptional consequences of trisomy 21 on neural induction.Frontiers in cellular neuroscience · 2024Article
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5 authors.
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Abstract
Introduction: Down syndrome (DS) is the most common genetic condition that causes intellectual disability in humans. The molecular mechanisms behind the DS phenotype remain unclear. Therefore, in this study, we present new findings on its molecular mechanisms through single-cell RNA sequencing. Methods: Induced pluripotent stem cells (iPSCs) from the patients with DS and the normal control (NC) patients were differentiated into iPSCs-derived neural stem cells (NSCs). Single-cell RNA sequencing was performed to achieve a comprehensive single-cell level differentiation roadmap for DS-iPSCs. Biological experiments were also performed to validate the findings. Results and Discussion: The results demonstrated that iPSCs can differentiate into NSCs in both DS and NC samples. Furthermore, 19,422 cells were obtained from iPSC samples (8,500 cells for DS and 10,922 cells for the NC) and 16,506 cells from NSC samples (7,182 cells for DS and 9,324 cells for the NC), which had differentiated from the iPSCs. A cluster of DS-iPSCs, named DS-iPSCs-not differentiated (DSi-PSCs-ND), which had abnormal expression patterns compared with NC-iPSCs, were demonstrated to be unable to differentiate into DS-NSCs. Further analysis of the differentially expressed genes revealed that inhibitor of differentiation family (ID family) members, which exhibited abnormal expression patterns throughout the differentiation process from DS-iPSCs to DS-NSCs, may potentially have contributed to the neural differentiation of DS-iPSCs. Moreover, abnormal differentiation fate was observed in DS-NSCs, which resulted in the increased differentiation of glial cells, such as astrocytes, but decreased differentiation into neuronal cells. Furthermore, functional analysis demonstrated that DS-NSCs and DS-NPCs had disorders in axon and visual system development. The present study provided a new insight into the pathogenesis of DS.
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