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

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...

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Autores principales:	Fabien Dachet, James B. Brown, Tibor Valyi-Nagy, Kunwar D. Narayan, Anna Serafini, Nathan Boley, Thomas R. Gingeras, Susan E. Celniker, Gayatry Mohapatra, Jeffrey A. Loeb
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1dbaf6e474940d2872df80387ee6579
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spelling	oai:doaj.org-article:f1dbaf6e474940d2872df80387ee65792021-12-02T17:04:05ZSelective time-dependent changes in activity and cell-specific gene expression in human postmortem brain10.1038/s41598-021-85801-62045-2322https://doaj.org/article/f1dbaf6e474940d2872df80387ee65792021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85801-6https://doaj.org/toc/2045-2322Abstract 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.Fabien DachetJames B. BrownTibor Valyi-NagyKunwar D. NarayanAnna SerafiniNathan BoleyThomas R. GingerasSusan E. CelnikerGayatry MohapatraJeffrey A. LoebNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabien Dachet James B. Brown Tibor Valyi-Nagy Kunwar D. Narayan Anna Serafini Nathan Boley Thomas R. Gingeras Susan E. Celniker Gayatry Mohapatra Jeffrey A. Loeb Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
description	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.
format	article
author	Fabien Dachet James B. Brown Tibor Valyi-Nagy Kunwar D. Narayan Anna Serafini Nathan Boley Thomas R. Gingeras Susan E. Celniker Gayatry Mohapatra Jeffrey A. Loeb
author_facet	Fabien Dachet James B. Brown Tibor Valyi-Nagy Kunwar D. Narayan Anna Serafini Nathan Boley Thomas R. Gingeras Susan E. Celniker Gayatry Mohapatra Jeffrey A. Loeb
author_sort	Fabien Dachet
title	Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
title_short	Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
title_full	Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
title_fullStr	Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
title_full_unstemmed	Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
title_sort	selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f1dbaf6e474940d2872df80387ee6579
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Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain

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