Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain.

Dachet, Fabien, Brown, James B, Valyi-Nagy, Tibor, Narayan, Kunwar D, Serafini, Anna, Boley, Nathan, Gingeras, Thomas R, Celniker, Susan E, Mohapatra, Gayatry, Loeb, Jeffrey A (March 2021) Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain. Scientific Reports, 11 (1). p. 6078. ISSN 2045-2322

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Abstract

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment diseases & disorders > mental disorders Investigative techniques and equipment > biomarker organs, tissues, organelles, cell types and functions > organs types and functions > brain bioinformatics > computational biology bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Gingeras, Thomas R.
Communities:	CSHL labs > Gingeras lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	23 March 2021
Date Deposited:	23 Apr 2021 16:33
Last Modified:	13 Feb 2024 16:41
PMCID:	PMC7988150
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39912

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