Cell-type-specific effects of age and sex on human cortical neurons

被引：10

作者：

Chien, Jo-Fan ^{[1
]}

Liu, Hanqing ^{[4
,5
]}

Wang, Bang-An ^{[4
,5
]}

Luo, Chongyuan ^{[4
,9
]}

Bartlett, Anna ^{[4
,5
]}

Castanon, Rosa ^{[4
,5
]}

Johnson, Nicholas D. ^{[2
,6
]}

Nery, Joseph R. ^{[4
,5
]}

Osteen, Julia ^{[4
,5
]}

Li, Junhao ^{[3
]}

Altshul, Jordan ^{[4
,5
]}

Kenworthy, Mia ^{[4
,5
]}

Valadon, Cynthia ^{[4
,5
]}

Liem, Michelle ^{[7
]}

Claffey, Naomi ^{[7
]}

O'Connor, Carolyn ^{[7
]}

Seeker, Luise A. ^{[8
]}

Ecker, Joseph R. ^{[4
,5
]}

Behrens, M. Margarita ^{[2
,6
]}

Mukamel, Eran A. ^{[3
]}

机构：

[1] Univ Calif San Diego, Dept Phys, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92037 USA

[4] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA

[5] Howard Hughes Med Inst, Salk Inst, La Jolla, CA 92037 USA

[6] Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA

[7] Salk Inst Biol Studies, Flow Cytometry Core Facil, La Jolla, CA 92037 USA

[8] Stanford Univ, Dept Bioengn, Stanford, CA USA

[9] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

来源：

NEURON | 2024年 / 112卷 / 15期

关键词：

DNA METHYLATION; REGULATORY ELEMENTS; TRANSCRIPTION; IDENTIFICATION; EXPRESSION; PATHOLOGY; ALIGNMENT; CLOCKS; CORTEX;

D O I：

10.1016/j.neuron.2024.05.013

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, , were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons.

引用

页码：2524 / 2539.e5

页数：22

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