Your browser doesn't support javascript.
loading
Cell-type-specific effects of age and sex on human cortical neurons.
Chien, Jo-Fan; Liu, Hanqing; Wang, Bang-An; Luo, Chongyuan; Bartlett, Anna; Castanon, Rosa; Johnson, Nicholas D; Nery, Joseph R; Osteen, Julia; Li, Junhao; Altshul, Jordan; Kenworthy, Mia; Valadon, Cynthia; Liem, Michelle; Claffey, Naomi; O'Connor, Carolyn; Seeker, Luise A; Ecker, Joseph R; Behrens, M Margarita; Mukamel, Eran A.
Afiliação
  • Chien JF; Department of Physics, University of California, San Diego, La Jolla, CA 92037, USA.
  • Liu H; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Wang BA; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Luo C; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Bartlett A; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Castanon R; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • 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.
  • Nery JR; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Osteen J; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Li J; Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA.
  • Altshul J; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Kenworthy M; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Valadon C; Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
  • Liem M; Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.
  • Claffey N; Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.
  • O'Connor C; Flow Cytometry Core Facility, Salk Institute, La Jolla, CA 92037, USA.
  • Seeker LA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • 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.
  • 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.
  • Mukamel EA; Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: emukamel@ucsd.edu.
Neuron ; 112(15): 2524-2539.e5, 2024 Aug 07.
Article em En | MEDLINE | ID: mdl-38838671
ABSTRACT
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.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metilação de DNA / Neurônios Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuron Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metilação de DNA / Neurônios Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuron Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos