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

DNA methylation EGR1 X inactivation aging epigenome frontal cortex sex differences single cell telomere transcriptome

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
31 May 2024
Historique:
received: 29 11 2023
revised: 29 03 2024
accepted: 09 05 2024
medline: 6 6 2024
pubmed: 6 6 2024
entrez: 5 6 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.neuron.2024.05.013 PMID: 38838671
pubmed: 38838671
pii: S0896-6273(24)00360-X
doi: 10.1016/j.neuron.2024.05.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.R.E. serves on the scientific advisory board of Zymo Research Inc.

Auteurs

Jo-Fan Chien (JF)

Department of Physics, University of California, San Diego, La Jolla, CA 92037, USA.

Hanqing Liu (H)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Bang-An Wang (BA)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Chongyuan Luo (C)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.

Anna Bartlett (A)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Rosa Castanon (R)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Nicholas D Johnson (ND)

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92037, USA; Computational Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037, USA.

Joseph R Nery (JR)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Julia Osteen (J)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Junhao Li (J)

Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA.

Jordan Altshul (J)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Mia Kenworthy (M)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Cynthia Valadon (C)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.

Michelle Liem (M)

Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.

Naomi Claffey (N)

Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.

Caz O'Connor (C)

Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.

Luise A Seeker (LA)

Department of Bioengineering, Stanford University, Stanford, CA, USA.

Joseph R Ecker (JR)

Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA. Electronic address: ecker@salk.edu.

M Margarita Behrens (MM)

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92037, USA; Computational Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037, USA. Electronic address: mbehrens@salk.edu.

Eran A Mukamel (EA)

Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: emukamel@ucsd.edu.

Classifications MeSH