Evidence map›Paper›PMID 36893254›Full record

ArticleScience (New York, N.Y.)2023

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

Michael A Wheeler, Iain C Clark, Hong-Gyun Lee, Zhaorong Li, Mathias Linnerbauer, Joseph M Rone, Manon Blain, Camilo Faust Akl, Gavin Piester, Federico Giovannoni and 21 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Astrocyte Functional Heterogeneity in Multiple Sclerosis.Journal of clinical neurology (Seoul, Korea) · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Michael A Wheeler *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-0689-6384
Iain C Clark *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9082-0253
Hong-Gyun Lee *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5960-5504
Zhaorong LiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5268-6986
Mathias LinnerbauerAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5528-5141
Joseph M RoneAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Manon BlainNeuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Camilo Faust AklAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5883-4441
Gavin PiesterAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-8413-7298
Federico GiovannoniAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Marc CharabatiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Joon-Hyuk LeeAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6249-4291
Yoon-Chul KyeAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-0261-5247
Joshua ChoiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Liliana M SanmarcoAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-2075-8826
Lena SrunAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Elizabeth N ChungAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lucas E FlausinoAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-2800-0374
Brian M AndersenAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1162-9061
Veit RothhammerAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hiroshi YanoJill 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.ORCID 0000-0002-3098-2629
Tomer IllouzAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-4123-6469
Stephanie E J ZandeeNeuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 0A9, Canada.
Carolin DanielType 1 Diabetes Immunology, Helmholtz Diabetes Center at Helmholtz Zentrum München, 80939 Munich, Germany.ORCID 0000-0003-4698-7069
David ArtisJill 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.ORCID 0000-0002-1753-4100
Marco PrinzInstitute of Neuropathology, University of Freiburg, D-79106 Freiburg, Germany.ORCID 0000-0002-0349-1955
Adam R AbateDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.ORCID 0000-0001-9614-4831
Vijay K KuchrooAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7177-2110
Jack P AntelNeuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.ORCID 0000-0002-5148-0636
Alexandre PratNeuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 0A9, Canada.ORCID 0000-0001-6188-0580
Francisco J QuintanaAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-8156-0736

Funding

Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
University of Rochester Mentoring Environment: Nurturing Training Opportunities in Research (UR-MENTOR)T32GM007356 · NIGMS · UNIVERSITY OF ROCHESTER · PI O'BANION, M. KERRY · 1985 to 2023
$15.1M
Project 2: Genes required for dendritic cell responses to pathogens and T cellsU19AI133524 · NIAID · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2017 to 2021
$12.3M
Neuroimmune Regulation of Atopic DermatitisR01AR070116 · NIAMS · WASHINGTON UNIVERSITY · PI KIM, BRIAN · 2016 to 2021
$3.8M
AHR-mediated immunosuppression in glioblastomaR01ES029136 · NIEHS · BRIGHAM AND WOMEN'S HOSPITAL · PI Francisco J. Quintana, DAVID A REARDON · 2019 to 2026
$3.3M
Decoding the language of inflammation between central nervous system resident immune cellsDP2AI154435 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI Iain Clark · 2021 to 2026
$2.4M
Control of extracellular matrix remodeling by CD29+ astrocytesR01MH130458 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI Michael Alex Wheeler · 2022 to 2026
$2.1M
Regulation of CNS AutoimmunityR01AI126880 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI QUINTANA, FRANCISCO J. · 2017 to 2021
$2.1M
Control of Local CNS InflammationR01NS102807 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI QUINTANA, FRANCISCO J. · 2018 to 2022
$1.8M
Pathogenic Astrocyte Populations in EAE and MSR01NS129778 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Francisco J. Quintana · 2023 to 2026
$1.7M
Molecular Control of Astrocytes in CNS InflammationR00NS114111 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI WHEELER, MICHAEL ALEX · 2023 to 2025
$783k
NCI NIH HHS K12 CA090354NIAID NIH HHS DP2 AI154435NIAID NIH HHS K22 AI152644NIAID NIH HHS P01 AI056299NIAID NIH HHS R01 AI126880NIAID NIH HHS U19 AI133524NIAMS NIH HHS R01 AR070116NIEHS NIH HHS R01 ES029136NIGMS NIH HHS T32 GM007356NIMH NIH HHS R01 MH130458NINDS NIH HHS F32 NS101790NINDS NIH HHS K99 NS114111NINDS NIH HHS R00 NS114111NINDS NIH HHS R01 NS102807NINDS NIH HHS R01 NS129778
6 · The paper itself

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.

Indexed as

AmphiregulinAstrocytesAutocrine CommunicationGenetic TestingMicrofluidic Analytical TechniquesMicrogliaGene ExpressionHigh-Throughput Screening AssaysHumansAmphiregulin

Identifiers

PMID36893254
PMCPMC10066924

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.