Transcriptomic homogeneity and an age-dependent onset of hemoglobin expression characterize morphological PV types

Abstract

The diversity created by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. For example, parvalbumin interneurons (PV-INs) comprise of a main transcriptomic cluster within all inhibitory cells. However, transcriptomics alone has not resolved the different morphological PV types that exist. To close this gap, we used single-cell RNA-seq in morphologically identified PV-INs, sampled from 10 days to 3 months-old mice and studied their transcriptomic states in the morphological, physiological, and developmental domains. Our findings reveal novel genes whose expression separately identify morphological types but corroborate an overall transcriptomic homogeneity among PV-INs. Surprisingly, morphological PV types display uniform cell adhesion molecule (CAM) profiles, suggesting that CAMs do not actively maintain their specificity of wiring after development. Finally, our results reveal a pronounced change of transcriptomic states between postnatal days 20 and 25, during which PV-INs display a rapid and unexpected onset of hemoglobin gene expression which remains stable in later development.