Neuron–Glia-Ratio-Like Approach Evidenced for Limited Variability and In-Aggregate Circadian Shifts in Cortical Cell-Specific Transcriptomes

• Published in: Journal of molecular neuroscience Vol. 73; no. 2-3; pp. 159 - 170
• Main Authors: Shchepina, Olesya A., Menshanov, Petr N.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2023; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell number; Cerebral Cortex; Circadian rhythm; Circadian rhythms; Consortia; Datasets; Depletion; Gene Expression Profiling; Glial cells; Humans; Ischemia; Microglia; Mutation; Neurochemistry; Neuroglia; Neurology; Neuronal-glial interactions; Neurons; Neurons - physiology; Neurosciences; Proteomics; Ratios; Transcriptome; Transcriptomes; Transcriptomics; Variability; Glia-neuron ratio; Cell-specific; Statistical precision; Univariate median; Transcriptome; Production–possibility frontier
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-023-02103-4

Regardless of shifts in levels of individual transcripts, it remains elusive whether natural variability in cell-specific transcriptomes within the cerebral cortex is limited in aggregate. It is also unclear whether cortical cell-specific transcriptomes might change dynamically in absence of cell number changes. Total variation in neuron- and glia-specific in-aggregate transcriptomes could be identified in a model-free way via glia-neuron ratio approach, by univariate median-to-median ratios comparing integral levels of cell-specific transcripts within a tissue sample. When deleterious, regenerative or developmental events affecting cortical cell numbers were subtle, median-to-median ratios demonstrated within-group variability not exceeding <20–25% in most cases. These levels of total variability might be explained in part by limited (~5–10%) circadian and stress-induced shifts in cell-specific cortical transcriptomes. Relevant in-aggregate transcriptomic alterations were identified after shifts in cell numbers induced by well-validated deleterious events including ischemia, traumatic injury, microglia’s activation/depletion or specific mutations. Cortical median-to-median ratios also follow naturally occurring changes in the numbers of excitatory, inhibitory neurons and glial cells during perinatal brain development. These findings characterize cortical cell-specific transcriptomes as subjects to circadian shifts and lifetime events, urging the importance of reporting full details on an origin of any transcriptomic sample collected in vivo.