2025-10-15 マウントサイナイ医療システム(MSHS)
<関連情報>
- https://www.mountsinai.org/about/newsroom/2025/two-mount-sinai-research-papers-present-evidence-of-distinct-molecular-differences-between-brain-tissue-from-living-people-and-tissue-collected-after-death
- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0332651
- https://www.nature.com/articles/s41380-025-03163-1
生きたヒトの脳におけるRNAスプライシングとタンパク質発現の研究 A study of RNA splicing and protein expression in the living human brain
Brian H. Kopell,Deepak A. Kaji,Lora E. Liharska,Eric Vornholt,Anina Lund,Alice Hashemi,Ryan C. Thompson,Jessica S. Johnson,Nicole Bussola,Esther Cheng,You Jeong Park,Punit Shah,Weiping Ma, [ … ],Alexander W. Charney
PLOS One Published: October 9, 2025
DOI:https://doi.org/10.1371/journal.pone.0332651
Abstract
Due to the unavailability of living human brain tissue for molecular research, postmortem brain samples are currently the standard tissue source for molecular studies of the human brain. The Living Brain Project (LBP) was designed to test the assumption that the postmortem brain is an accurate molecular representation of in the living brain on multiple levels of molecular biology. Findings from previous LBP reports suggest that this assumption does not hold with respect to RNA transcript expression levels. Here, molecular differences between living and postmortem human prefrontal cortex tissues obtained for the LBP are corroborated through analyses of RNA splicing and protein expression data. Significant differences were observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, and (3) the patterns of co-expression between RNA transcripts and proteins. Taken together, this report corroborates the presence of widespread molecular differences between living and postmortem human brain tissues. These observations should be considered when designing and interpreting studies of human brain biology.
生きた人間の脳における遺伝子発現の研究 A study of gene expression in the living human brain
Lora E. Liharska,You Jeong Park,Kimia Ziafat,Lillian Wilkins,Hannah Silk,Lisa M. Linares,Ryan C. Thompson,Eric Vornholt,Brendan Sullivan,Vanessa Cohen,Prashant Kota,Claudia Feng,Esther Cheng,Jessica S. Johnson,Marysia-Kolbe Rieder,Jia Huang,Joseph Scarpa,Jairo Polanco,Emily Moya,Alice Hashemi,Matthew A. Levin,Girish N. Nadkarni,Robert Sebra,John F. Crary,… Alexander W. Charney
Molecular Psychiatry Published:23 August 2025
DOI:https://doi.org/10.1038/s41380-025-03163-1
Abstract
A goal of psychiatric research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors. An assumption underlying this practice is that gene expression in the postmortem human brain is an accurate representation of gene expression in the living human brain. This assumption – which, until now, had not been adequately tested – was tested by comparing human prefrontal cortex gene expression between 275 living samples and 243 postmortem samples. Expression levels differed significantly for nearly 80% of genes, and a systematic examination of alternative explanations for this observation determined that these differences are not explained by cell type composition, RNA quality, postmortem interval, age, medication, morbidity, symptom severity, tissue pathology, sample handling, batch effects, or computational methods utilized. Using gene expression data from two independent cohorts, the differences identified between living and postmortem samples were replicated and shown to be present in all brain cell types. Analyses integrating the data generated for this study with data from earlier studies that used tissue from postmortem brain donors showed that postmortem brain gene expression signatures of psychiatric and neurological illnesses, as well as of normal traits such as aging, may not always be accurate representations of these gene expression signatures in the living brain. By using tissue safely obtained from large cohorts of living people, future studies of the human brain have the potential to (1) determine the biomedical research questions that can be addressed using postmortem tissue as a proxy for living tissue and (2) expand the scope of medical research to include questions about the molecular basis of human brain health and illness that can only be addressed in living people (e.g., “What happens in the brain at the molecular level as a person experiences an emotion?”).
