Droplet-based forward genetic screening of astrocyte–microglia cross-talk-Reference-Cited by-同舟云学术

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

Published:2023-03-10 Issue:6636 Volume:379 Page:1023-1030
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wheeler Michael A.¹²^ORCID,Clark Iain C.¹³^ORCID,Lee Hong-Gyun¹^ORCID,Li Zhaorong¹²^ORCID,Linnerbauer Mathias¹^ORCID,Rone Joseph M.¹,Blain Manon⁴,Akl Camilo Faust¹^ORCID,Piester Gavin¹⁵^ORCID,Giovannoni Federico¹,Charabati Marc¹,Lee Joon-Hyuk¹^ORCID,Kye Yoon-Chul¹⁶^ORCID,Choi Joshua¹⁶,Sanmarco Liliana M.¹^ORCID,Srun Lena¹,Chung Elizabeth N.¹,Flausino Lucas E.¹^ORCID,Andersen Brian M.¹⁷^ORCID,Rothhammer Veit¹⁸,Yano Hiroshi⁹^ORCID,Illouz Tomer¹^ORCID,Zandee Stephanie E. J.¹⁰,Daniel Carolin¹¹¹²¹³^ORCID,Artis David⁹¹⁴^ORCID,Prinz Marco¹⁵¹⁶¹⁷^ORCID,Abate Adam R.¹⁸¹⁹^ORCID,Kuchroo Vijay K.¹²⁶^ORCID,Antel Jack P.⁴^ORCID,Prat Alexandre¹⁰^ORCID,Quintana Francisco J.¹²^ORCID

Affiliation:

1. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

2. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. Department of Bioengineering, College of Engineering, California Institute for Quantitative Biosciences, University of California Berkeley, Berkeley, CA 94720, USA.

4. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.

5. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.

6. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.

7. Department of Neurology, Jamaica Plain Veterans Affairs Hospital, Harvard Medical School, Boston, MA 02130, USA.

8. Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany.

9. 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.

10. Neuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 0A9, Canada.

11. Type 1 Diabetes Immunology, Helmholtz Diabetes Center at Helmholtz Zentrum München, 80939 Munich, Germany.

12. Deutsches Zentrum für Diabetesforschung, 85764 Munich-Neuherberg, Germany.

13. Division of Clinical Pharmacology, Department of Medicine IV, Ludwig-Maximilians-Universität München, 80337 Munich, Germany.

14. Friedman Center for Nutrition and Inflammation, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.

15. Institute of Neuropathology, University of Freiburg, D-79106 Freiburg, Germany.

16. Signaling Research Centres BIOSS and CIBSS, University of Freiburg, D-79106 Freiburg, Germany.

17. Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany.

18. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.

19. Chan Zuckerberg Biohub, San Francisco, CA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abq4822

Reference94 articles.

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2. Astrocyte-immune cell interactions in physiology and pathology

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4. Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

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