AI Article Synopsis

  • * Stem cells from human exfoliated deciduous teeth (SHEDs) showed potential as a model for studying HCMV-related neural differentiation disorders since they can be easily infected by the virus.
  • * HCMV infection in SHEDs disrupts neural cell development, primarily by lowering cholesterol levels and impairing the function of SREBP2, a key regulator for cholesterol synthesis, which may provide new strategies for addressing related nervous system diseases.

Article Abstract

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335213PMC
http://dx.doi.org/10.1007/s00018-024-05278-0DOI Listing

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