Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic...

Area of Science:

• Neuroscience
• Developmental Biology
• Toxicology

Background:

• Early-life stress and environmental chemical exposure are linked to late-life neurological disorders.
• Human embryonic stem cell (hESC)-derived neural spheres offer a model for studying neurodevelopment and chemical safety.

Purpose of the Study:

• To investigate the neurodevelopmental effects of thalidomide (TMD), tetrabromodiphenyl ether, bisphenol A, and PCB congener on hESC-derived neural spheres.
• To identify molecular events and gene expression changes associated with chemical exposure during neural differentiation.

Main Methods:

• Utilized hESC-derived 3D neural sphere cultures for chemical exposure.
• Performed global gene expression profiling (microarray) and morphological examination of neural differentiation.
• Conducted transcriptomic analysis, functional annotation, and computational network analysis.

Main Results:

• Thalidomide (TMD) exposure significantly impacted neuronal differentiation in hESC-derived spheres.
• Transcriptomic analysis revealed TMD-induced genes associated with ERK and synaptic signaling pathways.
• Network analysis identified DNA-binding protein inhibitor ID2 as a key TMD-induced gene crucial for neuronal development.

Conclusions:

• Early-life transcriptomic changes induced by TMD exposure during hESC differentiation influence later-stage neuronal development.
• The hESC-derived sphere model is effective for assessing the neurodevelopmental toxicity of environmental chemicals.
• Findings highlight specific molecular pathways affected by TMD, providing insights into neurodevelopmental disorders.