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Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging

BACKGROUND: With the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for sever...

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Autores principales: Niu, Rui-Ze, Feng, Wan-Qing, Yu, Qing-Shan, Shi, Lan-Lan, Qin, Qing-Min, Liu, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394382/
https://www.ncbi.nlm.nih.gov/pubmed/37539343
http://dx.doi.org/10.3389/fnagi.2023.1063861
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author Niu, Rui-Ze
Feng, Wan-Qing
Yu, Qing-Shan
Shi, Lan-Lan
Qin, Qing-Min
Liu, Jia
author_facet Niu, Rui-Ze
Feng, Wan-Qing
Yu, Qing-Shan
Shi, Lan-Lan
Qin, Qing-Min
Liu, Jia
author_sort Niu, Rui-Ze
collection PubMed
description BACKGROUND: With the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for several neuropsychiatric disorders and for most neurodegenerative diseases characterized by onset typically occurring late in life and with worsening of symptoms over time. Therefore, the early prevention and intervention of aging progression are particularly important. Since there is no unified conclusion about the plasma diagnostic biomarkers of brain aging, this paper innovatively employed the combined multi-omics analysis to delineate the plasma markers of brain aging. METHODS: In order to search for specific aging markers in plasma during cerebral cortex aging, we used multi-omics analysis to screen out differential genes/proteins by integrating two prefrontal cortex (PFC) single-nucleus transcriptome sequencing (snRNA-seq) datasets and one plasma proteome sequencing datasets. Then plasma samples were collected from 20 young people and 20 elder people to verify the selected differential genes/proteins with ELISA assay. RESULTS: We first integrated snRNA-seq data of the post-mortem human PFC and generated profiles of 65,064 nuclei from 14 subjects across adult (44–58 years), early-aging (69–79 years), and late-aging (85–94 years) stages. Seven major cell types were classified based on established markers, including oligodendrocyte, excitatory neurons, oligodendrocyte progenitor cells, astrocytes, microglia, inhibitory neurons, and endotheliocytes. A total of 93 cell-specific genes were identified to be significantly associated with age. Afterward, plasma proteomics data from 2,925 plasma proteins across 4,263 young adults to nonagenarians (18–95 years old) were combined with the outcomes from snRNA-seq data to obtain 12 differential genes/proteins (GPC5, CA10, DGKB, ST6GALNAC5, DSCAM, IL1RAPL2, TMEM132C, VCAN, APOE, PYH1R, CNTN2, SPOCK3). Finally, we verified the 12 differential genes by ELISA and found that the expression trends of five biomarkers (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) were correlated with brain aging. CONCLUSION: Five differentially expressed proteins (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) can be considered as one of the screening indicators of brain aging, and provide a scientific basis for clinical diagnosis and intervention.
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spelling pubmed-103943822023-08-03 Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging Niu, Rui-Ze Feng, Wan-Qing Yu, Qing-Shan Shi, Lan-Lan Qin, Qing-Min Liu, Jia Front Aging Neurosci Neuroscience BACKGROUND: With the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for several neuropsychiatric disorders and for most neurodegenerative diseases characterized by onset typically occurring late in life and with worsening of symptoms over time. Therefore, the early prevention and intervention of aging progression are particularly important. Since there is no unified conclusion about the plasma diagnostic biomarkers of brain aging, this paper innovatively employed the combined multi-omics analysis to delineate the plasma markers of brain aging. METHODS: In order to search for specific aging markers in plasma during cerebral cortex aging, we used multi-omics analysis to screen out differential genes/proteins by integrating two prefrontal cortex (PFC) single-nucleus transcriptome sequencing (snRNA-seq) datasets and one plasma proteome sequencing datasets. Then plasma samples were collected from 20 young people and 20 elder people to verify the selected differential genes/proteins with ELISA assay. RESULTS: We first integrated snRNA-seq data of the post-mortem human PFC and generated profiles of 65,064 nuclei from 14 subjects across adult (44–58 years), early-aging (69–79 years), and late-aging (85–94 years) stages. Seven major cell types were classified based on established markers, including oligodendrocyte, excitatory neurons, oligodendrocyte progenitor cells, astrocytes, microglia, inhibitory neurons, and endotheliocytes. A total of 93 cell-specific genes were identified to be significantly associated with age. Afterward, plasma proteomics data from 2,925 plasma proteins across 4,263 young adults to nonagenarians (18–95 years old) were combined with the outcomes from snRNA-seq data to obtain 12 differential genes/proteins (GPC5, CA10, DGKB, ST6GALNAC5, DSCAM, IL1RAPL2, TMEM132C, VCAN, APOE, PYH1R, CNTN2, SPOCK3). Finally, we verified the 12 differential genes by ELISA and found that the expression trends of five biomarkers (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) were correlated with brain aging. CONCLUSION: Five differentially expressed proteins (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) can be considered as one of the screening indicators of brain aging, and provide a scientific basis for clinical diagnosis and intervention. Frontiers Media S.A. 2023-07-19 /pmc/articles/PMC10394382/ /pubmed/37539343 http://dx.doi.org/10.3389/fnagi.2023.1063861 Text en Copyright © 2023 Niu, Feng, Yu, Shi, Qin and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Niu, Rui-Ze
Feng, Wan-Qing
Yu, Qing-Shan
Shi, Lan-Lan
Qin, Qing-Min
Liu, Jia
Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title_full Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title_fullStr Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title_full_unstemmed Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title_short Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
title_sort integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394382/
https://www.ncbi.nlm.nih.gov/pubmed/37539343
http://dx.doi.org/10.3389/fnagi.2023.1063861
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