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A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder

Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics and the contribution of individual cell types remains largely unknown. We present an in-depth analysis of...

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Hauptverfasser: Zillich, Eric (VerfasserIn) , Artioli, Annasara (VerfasserIn) , Rossetti, Andrea C. (VerfasserIn) , Avetyan, Diana (VerfasserIn) , Belschner, Hanna (VerfasserIn) , Frank, Josef (VerfasserIn) , Stein, Frank (VerfasserIn) , Schwarz, Jennifer J. (VerfasserIn) , Mechawar, Naguib (VerfasserIn) , Turecki, Gustavo (VerfasserIn) , Nöthen, Markus M. (VerfasserIn) , Hansson, Anita C. (VerfasserIn) , Witt, Christian (VerfasserIn) , Rietschel, Marcella (VerfasserIn) , Koch, Philipp (VerfasserIn) , Spanagel, Rainer (VerfasserIn) , Zillich, Lea (VerfasserIn) , Witt, Stephanie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 25 February 2025
In: Cell reports
Year: 2025, Jahrgang: 44, Heft: 2, Pages: 1-27
ISSN:2211-1247
DOI:10.1016/j.celrep.2025.115332
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2025.115332
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124725001032
Volltext
Verfasserangaben:Eric Zillich, Annasara Artioli, Andrea C. Rossetti, Diana Avetyan, Hanna Belschner, Josef Frank, Frank Stein, Jennifer J. Schwarz, Naguib Mechawar, Gustavo Turecki, Markus M. Nöthen, Anita C. Hansson, Christian C. Witt, Marcella Rietschel, Philipp Koch, Rainer Spanagel, Lea Zillich, and Stephanie H. Witt
Beschreibung
Zusammenfassung:Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics and the contribution of individual cell types remains largely unknown. We present an in-depth analysis of molecular changes in the ventral striatum in CUD at multi-omics and single-cell resolution. Integrative multi-omics analyses of microRNA sequencing (microRNA-seq), RNA sequencing (RNA-seq), and proteomics datasets in 41 individuals and single-nuclei RNA-seq in a subset of 16 individuals revealed conserved deregulation of metabolic pathways, oxidative phosphorylation, and glutamatergic signaling. Cell type-specific analyses identified inverse metabolic pathway deregulation patterns in glial and neuronal cells, notably in astrocytes and medium-spiny neurons (MSNs). Characterizing astrocyte-neuron crosstalk revealed altered glutamatergic and cell-cell adhesion signaling in CUD. By applying a comprehensive multi-omics analytical framework, our study provides novel insights into CUD-associated molecular changes in the ventral striatum highlighting the perturbation of astrocytes, MSNs, and their crosstalk in CUD.
Beschreibung:Online verfügbar: 15. February 2025, Artikelversion: 15. Februar 2025
Gesehen am 24.07.2025
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2025.115332

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