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Concerted neuron-astrocyte gene expression declines in aging 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; French, 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 02142, USA.
  • Nemesh J; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Goldman M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kamitaki N; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Reed N; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Handsaker RE; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Genovese G; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Vogelgsang JS; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Gerges S; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Kashin S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ghosh S; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Esposito JM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • French K; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Meyer D; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lutservitz A; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Mullally CD; McLean Hospital, Belmont, MA 02478, USA.
  • Wysoker A; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
  • Spina L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Neumann A; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Hogan M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ichihara K; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Berretta S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • McCarroll SA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv ; 2024 Jan 08.
Article en En | MEDLINE | ID: mdl-38260461
ABSTRACT
Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a striking relationship between people's cortical neurons and cortical astrocytes. We used single-nucleus RNA-seq to analyze the prefrontal cortex of 191 human donors ages 22-97 years, including healthy individuals and persons with schizophrenia. Latent-factor analysis of these data revealed that in persons whose cortical neurons more strongly expressed genes for 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 aging - two conditions that involve declines in cognitive flexibility and plasticity 1,2 - cells had divested from SNAP astrocytes, glutamatergic (excitatory) neurons, and GABAergic (inhibitory) neurons all 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 persons of similar age, may underlie many aspects of normal human interindividual differences and be an important point of convergence for multiple kinds of pathophysiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos