Human organismal death initiates a state within the body wherein tissue components strive to survive by mounting the expression of developmental genes. This phenomenon offers an opportunity to gain insight into survival processes that are otherwise not manifested in the adult living body. Of outstanding interest is our observation that in humans such survival response is mounted following “slow” but not “fast” (traumatic) death. The scientific research to be conducted will develop an understanding of the ways in which cells and tissues, and the genes in them, strive for life even as the body dies. Skin is the largest organ of the human body, capable of sustaining life at a cellular level long after death. The proposed work will perform studies, using post-mortem skin (30-50 samples) from clinically and biologically dead organ donors undergoing organ and tissue procurement for transplantation by our surgeons. We hypothesize that some cells in the post-mortem skin are metaphorically and pedagogically sentient (i.e., able to anticipate the onset of death and therefore strive to kickstart regenerative/survival processes to overcome this onset). We label this subset of cells “resilient” and we hypothesize that such sentient responses are only set in motion when the body has sufficient time to prime itself for death (Hardy death scale 0, 4) as opposed to the onset of sudden death (Hardy scale 1,2). We propose to use three powerful technologies - single cell RNA sequencing, ATAC sequencing, and spatial analysis of gene expression to interrogate the skin samples. Taken together, these three data sets will validate each other and provide powerful insight into post-mortem skin tissue autopoiesis. Findings of the proposed work are likely to make a major impact on the overall conduct of biomedical research recognizing death as a biological variable in experimental studies. Finally, our findings will open up new far-reaching questions addressing the definition of death.
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