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Trisomy 21 Disrupts Thyroid Hormones Signaling During Human iPSC-Derived Neural Differentiation In Vitro.


ABSTRACT: Thyroid hormones (THs) are essential for brain development, and their dysregulation is associated with cognitive deficits and neurodevelopmental disorders. Down syndrome (DS), caused by trisomy 21, is frequently associated with thyroid dysfunction and impaired neurogenesis. Here, we investigated THs signaling dynamics during neural differentiation using human induced pluripotent stem cells (hiPSCs) derived from individuals with DS and controls. We analyzed the gene expression of key THs regulators-deiodinases, transporters, and receptors-and downstream target genes in hiPSCs, hiPSC-derived neural progenitor cells (NPCs), hiPSC-derived astrocytes, and hiPSC-derived neurons. DS-derived hiPSCs, hiPSC-derived NPCs, and hiPSC-derived neurons exhibited 2- to 7-fold increases in the gene expressi

SUBMITTER: de Souza JS 

PROVIDER: S-EPMC12468339 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature