Cytomegalovirus Infection in Human Cortical Organoids Induces Unique Developmental and Viral Substates

HCMV infection of human iPSC-derived cortical organoids reshapes 16 uninfected cell-type clusters and reveals multiple GFP-linked viral sub-states, including EMT-associated programs.

• Why it matters: Host tropism and brain anatomy limit how well HCMV replication and CNS impact can be studied, especially during development and in adult CNS disease contexts.
• What they did: Using single-cell RNA sequencing of infected and uninfected organoids, the authors mapped altered clusters and introduced a temporal class (TC) indexing score to model infection-stage variation across cells.
• The result: Machine learning identified cells likely producing de novo HCMV and viral sub-states enriched for EMT genes, with EpCAM protein induction independently verified in cortical organoids and glutamatergic neurons.

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