Genes of the undead: hibernation and death display different gene profiles

Hadj‐Moussa, Hanane; Watts, A.; Storey, Kenneth B.

doi:10.1002/1873-3468.13338

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…Therefore, while we studied the effect of simulated PMI at room temperature, in most cases following death the brain will be at a much higher temperature for a longer period than we used in our study here and therefore would likely have more rapid changes. While some studies have suggested that the RNA transcriptome is stable up to 30 h after death 23,30 , dynamic changes in RNA levels for specific cell types described here as a result of the PMI have been reported by others showing RNA degradation 31 , chromatin modification 6 , activation of gene expression [32][33][34] , and protein degradation 22 . While we did not directly look at protein expression, the predicted cell differences implicating specific cell populations would likely create corresponding proteomic changes in glia and neuronal cell populations.…”

Section: Discussionmentioning

confidence: 57%

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

Dachet

Brown

Vályi-Nagy

et al. 2021

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 57%

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

Dachet

Brown

Vályi-Nagy

et al. 2021

Sci Rep

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“…In fact, some biomolecules (e.g., caspases) can be activated even during the post-mortem period, showing that death is a dynamic process 5 . RNA degradation and synthesis after death has been investigated in the past 2 , 3 , 6 . However, most of the available data refer to studies that aimed to unravel molecular mechanisms of mental disorders, such as schizophrenia, Alzheimer and drug addiction 7 – 9 and little is known about how these processes occur in healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

Insights into how environment shapes post-mortem RNA transcription in mouse brain

Bonadio

Nunes

Moretti

et al. 2021

Sci Rep

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Most biological features that occur on the body after death were already deciphered by traditional medicine. However, the molecular mechanisms triggered in the cellular microenvironment are not fully comprehended yet. Previous studies reported gene expression alterations in the post-mortem condition, but little is known about how the environment could influence RNA degradation and transcriptional regulation. In this work, we analysed the transcriptome of mouse brain after death under three concealment simulations (air exposed, buried, and submerged). Our analyses identified 2,103 genes differentially expressed in all tested groups 48 h after death. Moreover, we identified 111 commonly upregulated and 497 commonly downregulated genes in mice from the concealment simulations. The gene functions shared by the individuals from the tested environments were associated with RNA homeostasis, inflammation, developmental processes, cell communication, cell proliferation, and lipid metabolism. Regarding the altered biological processes, we identified that the macroautophagy process was enriched in the upregulated genes and lipid metabolism was enriched in the downregulated genes. On the other hand, we also described a list of biomarkers associated with the submerged and buried groups, indicating that these environments can influence the post-mortem RNA abundance in its particular way.

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“…It has been widely assumed that death rapidly causes a complete shutdown of all molecular activities including transcription, translation, protein modifications and signalling cascades. This is definitely not the case [ 2 , 3 , 4 , 5 ], however, with the post-mortem proteome representing an intriguing map of the potential of a biological system. In living organisms, the decommissioning of cells occurs due to precisely expressed genetic and epigenetic controls that reduce the risk of the accumulation of damaged cells [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome

Wasinger

Curnoe

Boel

et al. 2020

IJMS

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The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of “death” pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through “deep-time” of individuals with no historically recorded cause of death.

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Genes of the undead: hibernation and death display different gene profiles

Cited by 6 publications

References 21 publications

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

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

Insights into how environment shapes post-mortem RNA transcription in mouse brain

The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome

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