Evidence map›Paper›PMID 36303069›Full record

ArticleNature neuroscience2022

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

Kun Leng, Indigo V L Rose, Hyosung Kim, Wenlong Xia, Wilber Romero-Fernandez, Brendan Rooney, Mark Koontz, Emmy Li, Yan Ao, Shinong Wang and 10 more

Open access · greenAbstract read
In one paragraph

Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 4 pooled it
12.5field-weighted citation impact, top 1% of its field
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

114 citing papers in PubMed, 4 syntheses or guidelines pooled it, 151 citations in OpenAlex.

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  17. bioRxiv : the preprint server for biology · 2026
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54 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

20 authors at 6 institutions in 1 country.

Kun LengInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA. kun.leng@ucsf.edu.ORCID http://orcid.org/0000-0001-9931-1375
Indigo V L RoseInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0491-1269
Hyosung KimDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Wenlong XiaDepartments of Neurology and Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Wilber Romero-FernandezDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Brendan RooneyInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Mark KoontzDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Emmy LiInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Yan AoDepartment of Neurobiology, University of California, Los Angeles, Los Angeles, CA, USA.
Shinong WangDepartment of Neurobiology, University of California, Los Angeles, Los Angeles, CA, USA.
Mitchell KrawczykInterdepartmental PhD Program in Neuroscience, University of California, Los Angeles, Los Angeles, CA, USA.
Julia TcwDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Alison GoateNash Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0576-2472
Ye ZhangDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-1546-5930
Erik M UllianDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2077-8584
Michael V SofroniewDepartment of Neurobiology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-6075-0178
Stephen P J FancyDepartments of Neurology and Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2818-8258
Matthew S SchragDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ethan S LippmannDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-5703-5747
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA. martin.kampmann@ucsf.edu.ORCID http://orcid.org/0000-0002-3819-7019
University of California, San Francisco · USUniversity of California, Los Angeles · USVanderbilt University · USBoston University · USIcahn School of Medicine at Mount Sinai · USVanderbilt University Medical Center · US

Funding

Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0M
Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 1985 to 2024
$16.8M
Regulation of Cellular Pathwaysin Human Brain DevelopmentP01NS083513 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALVAREZ-BUYLLA, ARTURO · 2014 to 2024
$12.6M
Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3M
Predoctoral Training in NeurobiologyT32NS115706 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMUEL JEREMY PLEASURE · 2020 to 2026
$3.4M
Injectable biomaterial depots to manipulate scar and foster axon growth after SCIR01NS084030 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SOFRONIEW, MICHAEL V · 2014 to 2023
$3.0M
Vasculature provides the substrate for oligodendrocyte progenitor migration in development and diseaseR01NS097551 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FANCY, STEPHEN PHILIP JAMES · 2017 to 2021
$1.7M
Deciphering isogenic APOE isoform dependent neurodegenerative response in human gliaK01AG062683 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TCW, JULIA · 2019 to 2023
$621k
Oligodendroglial Intrinsic Ring Finger Protein family members are injury specific, but not developmental, regulators of oligodendrocyte maturationR21NS119954 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FANCY, STEPHEN PHILIP JAMES · 2020 to 2021
$444k
Developing astrocyte, neuron, and microglial 3D organoids to model key aspects of human pathologyR03AG063157 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ULLIAN, ERIK M · 2019 to 2021
$333k
Elucidating cellular pathways controlling the reactive state of astrocytes in Alzheimer’s DiseaseF30AG066418 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LENG, KUN · 2019 to 2023
$155k
NEI NIH HHS P30 EY002162NIA NIH HHS F30 AG066418NIA NIH HHS K01 AG062683NIA NIH HHS P30 AG066514NIA NIH HHS R03 AG063157NICHD NIH HHS P50 HD103537NINDS NIH HHS P01 NS083513NINDS NIH HHS R01 NS084030NINDS NIH HHS R01 NS097551NINDS NIH HHS R21 NS119954NINDS NIH HHS T32 NS115706
6 · The paper itself

Abstract

Astrocytes become reactive in response to insults to the central nervous system by adopting context-specific cellular signatures and outputs, but a systematic understanding of the underlying molecular mechanisms is lacking. In this study, we developed CRISPR interference screening in human induced pluripotent stem cell-derived astrocytes coupled to single-cell transcriptomics to systematically interrogate cytokine-induced inflammatory astrocyte reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-κB activation drove two distinct inflammatory reactive signatures, one promoted by STAT3 and the other inhibited by STAT3. These signatures overlapped with those observed in other experimental contexts, including mouse models, and their markers were upregulated in human brains in Alzheimer's disease and hypoxic-ischemic encephalopathy. Furthermore, we validated that markers of these signatures were regulated by STAT3 in vivo using a mouse model of neuroinflammation. These results and the platform that we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAstrocytesCytokinesHumansInflammationSignal TransductionCytokines

Identifiers

PMID36303069
PMCPMC9633461
OpenAlexW4307493594

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.