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Droplet-based forward genetic screening of astrocyte-microglia cross-talk.
Wheeler, Michael A; Clark, Iain C; Lee, Hong-Gyun; Li, Zhaorong; Linnerbauer, Mathias; Rone, Joseph M; Blain, Manon; Akl, Camilo Faust; Piester, Gavin; Giovannoni, Federico; Charabati, Marc; Lee, Joon-Hyuk; Kye, Yoon-Chul; Choi, Joshua; Sanmarco, Liliana M; Srun, Lena; Chung, Elizabeth N; Flausino, Lucas E; Andersen, Brian M; Rothhammer, Veit; Yano, Hiroshi; Illouz, Tomer; Zandee, Stephanie E J; Daniel, Carolin; Artis, David; Prinz, Marco; Abate, Adam R; Kuchroo, Vijay K; Antel, Jack P; Prat, Alexandre; Quintana, Francisco J.
Afiliación
  • Wheeler MA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Clark IC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lee HG; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Li Z; Department of Bioengineering, College of Engineering, California Institute for Quantitative Biosciences, University of California Berkeley, Berkeley, CA 94720, USA.
  • Linnerbauer M; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Rone JM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Blain M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Akl CF; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Piester G; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Giovannoni F; Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
  • Charabati M; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Lee JH; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Kye YC; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • Choi J; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Sanmarco LM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Srun L; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chung EN; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Flausino LE; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Andersen BM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Rothhammer V; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Yano H; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Illouz T; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Zandee SEJ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Daniel C; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Artis D; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Prinz M; Department of Neurology, Jamaica Plain Veterans Affairs Hospital, Harvard Medical School, Boston, MA 02130, USA.
  • Abate AR; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Kuchroo VK; Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany.
  • Antel JP; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
  • Prat A; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Quintana FJ; Neuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 0A9, Canada.
Science ; 379(6636): 1023-1030, 2023 03 10.
Article en En | MEDLINE | ID: mdl-36893254
ABSTRACT
Cell-cell interactions in the central nervous system play important roles in neurologic diseases. However, little is known about the specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture in picoliter droplets, and microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell-cell communication. We used SPEAC-seq (systematic perturbation of encapsulated associated cells followed by sequencing), in combination with in vivo genetic perturbations, to identify microglia-produced amphiregulin as a suppressor of disease-promoting astrocyte responses in multiple sclerosis preclinical models and clinical samples. Thus, SPEAC-seq enables the high-throughput systematic identification of cell-cell communication mechanisms.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pruebas Genéticas / Astrocitos / Microglía / Comunicación Autocrina / Técnicas Analíticas Microfluídicas / Anfirregulina Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
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PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pruebas Genéticas / Astrocitos / Microglía / Comunicación Autocrina / Técnicas Analíticas Microfluídicas / Anfirregulina Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos