TY - JOUR

T1 - Neuron-Glia-Ratio-Like Approach Evidenced for Limited Variability and In-Aggregate Circadian Shifts in Cortical Cell-Specific Transcriptomes

AU - Shchepina, Olesya A

AU - Menshanov, Petr N

N1 - Funding: This work was supported by Novosibirsk State University [2021–2030]. Access to databases was provided by the Novosibirsk State University and Novosibirsk State Technical University. © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2023/3

Y1 - 2023/3

N2 - 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.

AB - 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.

KW - Cell-specific

KW - Glia-neuron ratio

KW - Production–possibility frontier

KW - Statistical precision

KW - Transcriptome

KW - Univariate median

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85147589819&origin=inward&txGid=63bd47deb6e518515da7fb7a8ed74dc2

UR - https://www.mendeley.com/catalogue/65cf9485-dbad-32cb-91ea-5fa181ac6048/

U2 - 10.1007/s12031-023-02103-4

DO - 10.1007/s12031-023-02103-4

M3 - Article

C2 - 36745298

VL - 73

SP - 159

EP - 170

JO - Journal of molecular neuroscience

JF - Journal of molecular neuroscience

SN - 0895-8696

IS - 2-3

ER -