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Wheeler, M.A.* ; Clark, I.C.* ; Lee, H.G.* ; Li, Z.* ; Linnerbauer, M.* ; Rone, J.M.* ; Blain, M.* ; Akl, C.F.* ; Piester, G.* ; Giovannoni, F.* ; Charabati, M.* ; Lee, J.H.* ; Kye, Y.C.* ; Choi, J.* ; Sanmarco, L.M.* ; Srun, L.* ; Chung, E.N.* ; Flausino, L.E.* ; Andersen, B.M.* ; Rothhammer, V.* ; Yano, H.* ; Illouz, T.* ; Zandee, S.E.J.* ; Daniel, C. ; Artis, D.* ; Prinz, M.* ; Abate, A.R.* ; Kuchroo, V.K.* ; Antel, J.P.* ; Prat, A.* ; Quintana, F.J.*

Droplet-based forward genetic screening of astrocyte-microglia cross-talk.

Science 379, 1023-1030 (2023)
DOI PMC
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Regulatory T-cells; In-vivo; Il-33 Promotes; Inflammation; System; Amphiregulin; Macrophages; Dna
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 379, Issue: 6636, Pages: 1023-1030 Article Number: , Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Type 1 Diabetes Immunology (TDI)
Grants Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education
Women's Brain Initiative at Brigham and Women's Hospital
Program in Interdisciplinary Neuroscience at Brigham and Women's Hospital
Dana-Farber Cancer Institute
International Progressive MS Alliance
American Cancer Society
NMSS
NIH

EMBO postdoctoral fellowship
Crohn's and Colitis Foundation
NRF of Korea
EFSD/JDRF/Lilly Programme on Type 1 Diabetes Research 2020
Deutsche Forschungsgemeinschaft
German Center for Diabetes Research (DZD)
Research Division (TDI) at Helmholtz Zentrum Munchen
Excellence Program for Outstanding Female Scientists from the Helmholtz Association
Canadian Foundation for Innovation
Canada Institute of Health Research
FRQS/MSSC Partnership Award
Ministry of Education