Droplet-based forward genetic screening of astrocyte-microglia cross-talk.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
10 03 2023
10 03 2023
Historique:
entrez:
9
3
2023
pubmed:
10
3
2023
medline:
14
3
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36893254
doi: 10.1126/science.abq4822
pmc: PMC10066924
mid: NIHMS1883502
doi:
Substances chimiques
Amphiregulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1023-1030Subventions
Organisme : NIMH NIH HHS
ID : R01 MH130458
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI056299
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS114111
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI154435
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS101790
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA090354
Pays : United States
Organisme : NINDS NIH HHS
ID : R00 NS114111
Pays : United States
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