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Single-cell multi-cohort dissection of the schizophrenia transcriptome.

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  • معلومة اضافية
    • Corporate Authors:
      PsychENCODE Consortium§; PsychENCODE Consortium
    • المصدر:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
    • بيانات النشر:
      Publication: : Washington, DC : American Association for the Advancement of Science
      Original Publication: New York, N.Y. : [s.n.] 1880-
    • الموضوع:
      Genetic Predisposition to Disease* ; Neurons*/metabolism ; Prefrontal Cortex*/metabolism ; Schizophrenia*/genetics ; Single-Cell Analysis* ; Neuroglia*/metabolism; Adult ; Female ; Humans ; Male ; Cohort Studies ; Risk Factors ; Synapses/metabolism ; Transcriptome ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over
    • نبذة مختصرة :
      The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective therapies. Here, we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across 140 individuals in two independent cohorts. Excitatory neurons were the most affected cell group, with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways. Transcriptional alterations included known genetic risk factors, suggesting convergence of rare and common genomic variants on neuronal population-specific alterations in schizophrenia. Based on the magnitude of schizophrenia-associated transcriptional change, we identified two populations of individuals with schizophrenia marked by expression of specific excitatory and inhibitory neuronal cell states. This single-cell atlas links transcriptomic changes to etiological genetic risk factors, contextualizing established knowledge within the human cortical cytoarchitecture and facilitating mechanistic understanding of schizophrenia pathophysiology and heterogeneity.
    • Grant Information:
      K08 MH122911 United States MH NIMH NIH HHS; U01 MH122681 United States MH NIMH NIH HHS
    • Contributed Indexing:
      Investigator: S Akbarian; A Abyzov; N Ahituv; D Arasappan; JJ Almagro Armenteros; BJ Beliveau; S Berretta; RA Bharadwaj; A Bhattacharya; L Bicks; K Brennand; D Capauto; FA Champagne; T Chatterjee; C Chatzinakos; Y Chen; HI Chen; Y Cheng; L Cheng; A Chess; JF Chien; Z Chu; D Clarke; A Clement; L Collado-Torres; GM Cooper; GE Crawford; R Dai; NP Daskalakis; A Deep-Soboslay; C Deng; CP DiPietro; S Dracheva; S Drusinsky; Z Duan; D Duong; C Dursun; NJ Eagles; J Edelstein; PS Emani; K Galani; T Galeev; MJ Gandal; S Gaynor; M Gerstein; DH Geschwind; K Girdhar; FS Goes; W Greenleaf; J Grundman; H Guo; Q Guo; C Gupta; Y Hadas; J Hallmayer; X Han; N Hawken; C He; E Henry; SC Hicks; M Ho; LL Ho; Y Huang; LA Huuki-Myers; A Hwang; TM Hyde; A Iatrou; F Inoue; A Jajoo; M Jensen; L Jiang; P Jin; T Jin; C Jops; A Jourdon; R Kawaguchi; JE Kleinman; SP Kleopoulos; A Kozlenkov; A Kriegstein; A Kundaje; S Kundu; C Lee; D Lee; J Li; M Li; X Lin; S Liu; J Liu; J Liu; C Liu; S Liu; S Lou; JM Loupe; D Lu; S Ma; L Ma; M Margolis; J Mariani; K Martinowich; KR Maynard; S Mazariegos; R Meng; RM Myers; C Micallef; T Mikhailova; GL Ming; E Monte; KS Montgomery; JE Moore; JR Moran; EA Mukamel; AC Nairn; CB Nemeroff; P Ni; S Norton; T Nowakowski; L Omberg; SC Page; S Park; A Patowary; R Pattni; G Pertea; MA Peters; N Phalke; D Pinto; M Pjanic; S Pochareddy; KS Pollard; A Pollen; H Pratt; PF Przytycki; C Purmann; ZS Qin; PP Qu; D Quintero; T Raj; AS Rajagopalan; S Reach; T Reimonn; KJ Ressler; D Ross; J Rozowsky; M Ruth; SJ Sanders; JM Schneider; S Scuderi; R Sebra; N Sestan; N Seyfried; Z Shao; N Shedd; AW Shieh; JH Shin; M Skarica; C Snijders; H Song; MW State; J Stein; M Steyert; T Sudhof; M Snyder; R Tao; K Therrien; LH Tsai; AE Urban; FM Vaccarino; H van Bakel; D Vo; B Wamsley; T Wang; SH Wang; D Wang; Y Wang; J Warrell; Y Wei; AK Weimer; DR Weinberger; C Wen; Z Weng; S Whalen; KP White; AJ Willsey; H Won; W Wong; H Wu; F Wu; S Wuchty; D Wylie; S Xu; CX Yap; B Zeng; P Zhang; C Zhang; B Zhang; J Zhang; Y Zhang; X Zhou; R Ziffra; ZR Zeier; TM Zintel
    • الموضوع:
      Date Created: 20240523 Date Completed: 20240523 Latest Revision: 20241023
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.1126/science.adg5136
    • الرقم المعرف:
      38781388