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<p>Down syndrome (DS) is a relatively severe chromosomal disorder marked by multiple significant clinical abnormalities. Currently, there is a need for the development of novel screening methods that utilize ideal cells, animal models, and clinical samples. In this study, we collected residual samples from clinical chromosome karyotyping analyses. Utilizing reprogramming technology with four transcription factors—KLF4, OCT4, c-MYC, and SOX2—we successfully generated Down syndrome-specific induced pluripotent stem cells (iPSCs). Flow cytometry and G-banding karyotyping validation confirmed that all established cell lines expressed pluripotency markers (TRA-1-81, SSEA4) and retained the characteristic karyotype (47,XY,+21). Subsequently, we isolated exosomes from the culture supernatant of DS-iPSCs. Microarray analysis revealed 595 differentially expressed non-coding RNAs (ncRNA), comprising 210 upregulated and 175 downregulated pre-miRNAs, as well as 123 upregulated and 87 downregulated small nucleolar RNAs (snoRNAs). Functional enrichment analysis indicated that these ncRNAs are primarily involved in key biological processes such as gene silencing, gene expression regulation, and peptide biosynthesis. Structural similarity analysis suggested that <i>hsa-let-7c</i> shares primary and secondary structural features with certain snoRNAs. Reverse transcription droplet digital PCR (RT-ddPCR) validation confirmed the upregulation of multiple pre-miRNAs, including <i>hsa-let-7c</i>, in the peripheral blood of mothers carrying DS fetuses. Overall, this study suggests that exosomal ncRNAs derived from DS-iPSCs may serve as potential targets for future biomarker discovery in DS diagnosis. This finding offers a novel approach for biomarker screening in diseases where obtaining clinical samples is challenging.</p>

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Generation and Exosomal Noncoding RNA Profiling of Down Syndrome-Specific Induced Pluripotent Stem Cells

  • 期刊论文

  • 发表日期：

    2026年1月23日

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  • Chunxia Li,
  • Weiwei Gong,
  • Gengshuo Chen,
  • Yu Sha,
  • Chune Mo,
  • Jiajun Xu,
  • Xianliang Hou,
  • Minglin Ou

摘要

Down syndrome (DS) is a relatively severe chromosomal disorder marked by multiple significant clinical abnormalities. Currently, there is a need for the development of novel screening methods that utilize ideal cells, animal models, and clinical samples. In this study, we collected residual samples from clinical chromosome karyotyping analyses. Utilizing reprogramming technology with four transcription factors—KLF4, OCT4, c-MYC, and SOX2—we successfully generated Down syndrome-specific induced pluripotent stem cells (iPSCs). Flow cytometry and G-banding karyotyping validation confirmed that all established cell lines expressed pluripotency markers (TRA-1-81, SSEA4) and retained the characteristic karyotype (47,XY,+21). Subsequently, we isolated exosomes from the culture supernatant of DS-iPSCs. Microarray analysis revealed 595 differentially expressed non-coding RNAs (ncRNA), comprising 210 upregulated and 175 downregulated pre-miRNAs, as well as 123 upregulated and 87 downregulated small nucleolar RNAs (snoRNAs). Functional enrichment analysis indicated that these ncRNAs are primarily involved in key biological processes such as gene silencing, gene expression regulation, and peptide biosynthesis. Structural similarity analysis suggested that hsa-let-7c shares primary and secondary structural features with certain snoRNAs. Reverse transcription droplet digital PCR (RT-ddPCR) validation confirmed the upregulation of multiple pre-miRNAs, including hsa-let-7c, in the peripheral blood of mothers carrying DS fetuses. Overall, this study suggests that exosomal ncRNAs derived from DS-iPSCs may serve as potential targets for future biomarker discovery in DS diagnosis. This finding offers a novel approach for biomarker screening in diseases where obtaining clinical samples is challenging.