Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease

被引：4

作者：

Froehlich, Anna S. ^{[1
,2
]}

Gerstner, Nathalie ^{[1
,2
,3
]}

Gagliardi, Miriam ^{[4
]}

Koedel, Maik ^{[1
]}

Yusupov, Natan ^{[1
,2
]}

Matosin, Natalie ^{[5
,6
]}

Czamara, Darina ^{[1
]}

Sauer, Susann ^{[1
]}

Roeh, Simone ^{[1
]}

Murek, Vanessa ^{[4
]}

Chatzinakos, Chris ^{[7
,8
,9
]}

Daskalakis, Nikolaos P. ^{[7
,8
]}

Knauer-Arloth, Janine ^{[1
,3
]}

Ziller, Michael J. ^{[4
]}

Binder, Elisabeth B. ^{[1
,10
]}

机构：

[1] Max Planck Inst Psychiat, Dept Genes & Environm, Munich, Germany

[2] Int Max Planck Res Sch Translat Psychiat, Munich, Germany

[3] Helmholtz Zentrum Munchen, Inst Computat Biol, Neuherberg, Germany

[4] Univ Munster, Dept Psychiat, Munster, Germany

[5] Univ Sydney, Fac Med & Hlth, Sch Med Sci, Camperdown, NSW, Australia

[6] Univ Sydney, Charles Perkins Ctr, Camperdown, NSW, Australia

[7] Harvard Med Sch, McLean Hosp, Dept Psychiat, Belmont, MA USA

[8] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[9] SUNY Downstate Hlth Sci Univ, Inst Genom Hlth, Dept Psychiat & Behav Sci, Brooklyn, NY USA

[10] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

来源：

NATURE NEUROSCIENCE | 2024年 / 27卷 / 10期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION; QUANTILE NORMALIZATION; BIOCONDUCTOR PACKAGE; ALZHEIMERS-DISEASE; BRAIN; AGE; NEURODEGENERATION; ASSOCIATION; MICROGLIA; LINGO-1;

D O I：

10.1038/s41593-024-01742-z

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The risk for neurodegenerative disorders is also increased in individuals with psychiatric disorders. Here, we characterized age-related transcriptomic changes in the brain by profiling similar to 800,000 nuclei from the orbitofrontal cortex from 87 individuals with and without psychiatric diagnoses and replicated findings in an independent cohort with 32 individuals. Aging affects all cell types, with LAMP5(+)LHX6(+) interneurons, a cell-type abundant in primates, by far the most affected. Disrupted synaptic transmission emerged as a convergently affected pathway in aged tissue. Age-related transcriptomic changes overlapped with changes observed in Alzheimer's disease across multiple cell types. We find evidence for accelerated transcriptomic aging in individuals with psychiatric disorders and demonstrate a converging signature of aging and psychopathology across multiple cell types. Our findings shed light on cell-type-specific effects and biological pathways underlying age-related changes and their convergence with effects driven by psychiatric diagnosis.

引用

页码：2021 / 2032

页数：32

共 31 条

[31] Single-cell transcriptomic profiling reveals specific maturation signatures in human cardiomyocytes derived from LMNB2-inactivated induced pluripotent stem cells
Wang, Jie
Morgan, William
Saini, Ankur
Liu, Tao
Lough, John
Han, Lu
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2022, 10

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