Assessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoids

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dc.citation.articleNumbere202107135en_US
dc.citation.issueNumber4en_US
dc.citation.journalTitleJournal of Cell Biologyen_US
dc.citation.volumeNumber221en_US
dc.contributor.authorCvetkovic, Carolineen_US
dc.contributor.authorPatel, Rajanen_US
dc.contributor.authorShetty, Aryaen_US
dc.contributor.authorHogan, Matthew K.en_US
dc.contributor.authorAnderson, Morganen_US
dc.contributor.authorBasu, Nupuren_US
dc.contributor.authorAghlara-Fotovat, Samiraen_US
dc.contributor.authorRamesh, Srivathsanen_US
dc.contributor.authorSardar, Debosmitaen_US
dc.contributor.authorVeiseh, Omiden_US
dc.contributor.authorWard, Michael E.en_US
dc.contributor.authorDeneen, Benjaminen_US
dc.contributor.authorHorner, Philip J.en_US
dc.contributor.authorKrencik, Roberten_US
dc.date.accessioned2022-09-01T14:18:21Zen_US
dc.date.available2022-09-01T14:18:21Zen_US
dc.date.issued2022en_US
dc.description.abstractAstrocyte reactivity can directly modulate nervous system function and immune responses during disease and injury. However, the consequence of human astrocyte reactivity in response to specific contexts and within neural networks is obscure. Here, we devised a straightforward bioengineered neural organoid culture approach entailing transcription factor–driven direct differentiation of neurons and astrocytes from human pluripotent stem cells combined with genetically encoded tools for dual cell-selective activation. This strategy revealed that Gq-GPCR activation via chemogenetics in astrocytes promotes a rise in intracellular calcium followed by induction of immediate early genes and thrombospondin 1. However, astrocytes also undergo NF-κB nuclear translocation and secretion of inflammatory proteins, correlating with a decreased evoked firing rate of cocultured optogenetic neurons in suboptimal conditions, without overt neurotoxicity. Altogether, this study clarifies the intrinsic reactivity of human astrocytes in response to targeting GPCRs and delivers a bioengineered approach for organoid-based disease modeling and preclinical drug testing.en_US
dc.identifier.citationCvetkovic, Caroline, Patel, Rajan, Shetty, Arya, et al.. "Assessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoids." <i>Journal of Cell Biology,</i> 221, no. 4 (2022) Rockefeller University Press: https://doi.org/10.1083/jcb.202107135.en_US
dc.identifier.digitaljcb_202107135en_US
dc.identifier.doihttps://doi.org/10.1083/jcb.202107135en_US
dc.identifier.urihttps://hdl.handle.net/1911/113167en_US
dc.language.isoengen_US
dc.publisherRockefeller University Pressen_US
dc.rightsThis article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.titleAssessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoidsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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