A concerted neuron–astrocyte program declines in ageing and schizophrenia

Abstract Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this…

• MG
  Massachusetts General Hospital
• BI
  Broad Institute
• NI
  National Institutes of Health

  Awards: T32 HG002295, U01MH115727
• SC
  Stanley Center for Psychiatric Research, Broad Institute
• NI
  National Institute of Mental Health

  Awards: P50MH115874, U01MH115727