Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian mammals [Stereo-seq]

We used single-nucleus RNA sequencing and spatial transcriptomics to compare primary visual cortex in marsupial (opossum) and placental (mouse) mammals. Major neuronal subclasses and laminar architecture were broadly conserved, but intratelencephalic (IT) neurons differed markedly.

Opossum IT neurons exhibited more generalized, overlapping transcriptomic identities with a continuous spatio-transcriptomic gradient between superficial (L2/3) and deep (L5) IT populations, whereas mouse IT neurons showed sharper transcriptomic distinctions and greater spatial confinement, consistent with increased specialization. Mouse cortex also displayed reduced PV interneuron density and redistribution of perineuronal nets, suggesting altered constraints on cortical plasticity.