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A concerted neuron-astrocyte program declines in ageing and schizophrenia.
Ling, Emi; Nemesh, James; Goldman, Melissa; Kamitaki, Nolan; Reed, Nora; Handsaker, Robert E; Genovese, Giulio; Vogelgsang, Jonathan S; Gerges, Sherif; Kashin, Seva; Ghosh, Sulagna; Esposito, John M; Morris, Kiely; Meyer, Daniel; Lutservitz, Alyssa; Mullally, Christopher D; Wysoker, Alec; Spina, Liv; Neumann, Anna; Hogan, Marina; Ichihara, Kiku; Berretta, Sabina; McCarroll, Steven A.
Afiliación
  • Ling E; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. eling@broadinstitute.org.
  • Nemesh J; Department of Genetics, Harvard Medical School, Boston, MA, USA. eling@broadinstitute.org.
  • Goldman M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kamitaki N; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Reed N; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Handsaker RE; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Genovese G; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Vogelgsang JS; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Gerges S; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Kashin S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ghosh S; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Esposito JM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Morris K; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Meyer D; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lutservitz A; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Mullally CD; McLean Hospital, Belmont, MA, USA.
  • Wysoker A; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
  • Spina L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Neumann A; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Hogan M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ichihara K; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Berretta S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • McCarroll SA; Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nature ; 627(8004): 604-611, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38448582
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 relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing-two conditions that involve declines in cognitive flexibility and plasticity1,2-cells divested from SNAP astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esquizofrenia / Envejecimiento / Astrocitos / Corteza Prefrontal / Neuronas Límite: Aged80 Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esquizofrenia / Envejecimiento / Astrocitos / Corteza Prefrontal / Neuronas Límite: Aged80 Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos