Evidence map›Paper›PMID 34244682›Full record

ArticleNature medicine2021

A human three-dimensional neural-perivascular 'assembloid' promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology.

Lu Wang, David Sievert, Alex E Clark, Sangmoon Lee, Hannah Federman, Benjamin D Gastfriend, Eric V Shusta, Sean P Palecek, Aaron F Carlin, Joseph G Gleeson

Open access · bronzeAbstract read
In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
13.1field-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

99 citing papers in PubMed, 143 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  10. Article
  11. Multiscale Construction, Evaluation, and Application of Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  12. Article
  13. Review
  14. Organoids: physiologically relevantJournal of virology · 2025
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Lu WangDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
David SievertDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Alex E ClarkDepartment of Medicine, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Sangmoon LeeDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Hannah FedermanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Benjamin D GastfriendDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-4677-1455
Eric V ShustaDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Aaron F CarlinDepartment of Medicine, University of California San Diego, School of Medicine, La Jolla, CA, USA. acarlin@health.ucsd.edu.ORCID http://orcid.org/0000-0002-1669-8066
Joseph G GleesonDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA. jogleeson@health.ucsd.edu.ORCID http://orcid.org/0000-0002-0889-9220
Children’s Institute · USUniversity of Wisconsin–Madison · USRutgers, The State University of New Jersey · USUC San Diego Health System · USUniversity of California San Diego · US

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Molecular basis of Zika-induced microcephalyR01NS106387 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2018 to 2021
$2.2M
Investigating Pericyte Roles in Blood-Brain Barrier FormationR01NS103844 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SHUSTA, ERIC V · 2018 to 2022
$1.9M
Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infectionsK08AI130381 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARLIN, AARON F. · 2019 to 2023
$1.0M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
A Phenotypical Brain Organoids for Neurodevelopmental DisordersK99NS125106 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, LU · 2022 to 2023
$211k
Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) 28771NIAID NIH HHS K08 AI130381NIGMS NIH HHS T32 GM008349NIH HHS S10 OD026929NINDS NIH HHS K99 NS125106NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS103844NINDS NIH HHS R01 NS106387
6 · The paper itself

Abstract

Clinical evidence suggests the central nervous system is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although the mechanisms are unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Before infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral 'replication hubs', with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new 'assembloid' model that supports astrocytic maturation as well as SARS-CoV-2 entry and replication in neural tissue; thus, PCCOs serve as an experimental model for neural infection.

Indexed as

AstrocytesBrainCell DifferentiationCells, CulturedCOVID-19HumansInterferon Type IPericytesSARS-CoV-2Viral TropismVirus ReplicationInterferon Type I

Identifiers

PMID34244682
PMCPMC8601037
OpenAlexW3178716999

What OpenQuestion holds

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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.