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| Status |
Public on Sep 30, 2022 |
| Title |
SARS-CoV-2 infection of Lung Organoids Reveals Conserved Use of Tetraspanin-8 by Ancestral-, Delta-, and Omicron- Variants |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease variation linked to immune dysfunction. The mechanistic underpinnings of variation related to lung epithelium are relatively understudied. Here, we biobanked lung organoids by preserving stem cell function. We optimized viral infection with H1N1 swine flu and next comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable lung organoids from twenty different subjects. We discovered Tetraspanin 8 (TSPAN8) as a novel mediator of SARS-CoV-2-infection. TSPAN8 facilitates SARS-CoV-2 infection rates but does not via enhanced ACE-2-mediated entry. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta- and Omicron- VOC displayed lower overall infection rates of organoids but triggered increased epithelial interferon responses. All variants shared highest tropism for ciliated- and goblet- cells. ACE2- and TSPAN8- expression are universal features of infected cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.
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| Overall design |
2 multiplexed pools consisting of 8 total Lung organoids tagged with lipid-based Multiseq. Mock and SARS-SoC-2 infected organoids of 2522UL , 2450UL, L7UL, and 2524U
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| Contributor(s) |
Hysenaj L, Rodriguez L, Andersen C, Rao AA, Roose JP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 AI091580 |
Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR |
University of California San Francisco |
JEROEN ROOSE |
| P01 AI091580 |
Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR |
University of California San Francisco |
ARTHUR WEISS |
| U19 AI077439 |
Understanding Asthma Endotypes |
University of California San Francisco |
David J Erle |
| R37 AI083139 |
Role of Factor Acetylation in the Regulation of HIV Transcription |
J. DAVID GLADSTONE INSTITUTES |
Melanie Maria Ott |
| R35 HL145235 |
Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies |
University of California San Francisco |
David J Erle |
| R01 AI138546 |
Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq |
KWAZULU-NATAL RESEARCH INSTITUTE FOR TB-HIV (K-RITH) |
Alexander Sigal |
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| Submission date |
Aug 18, 2022 |
| Last update date |
Oct 02, 2022 |
| Contact name |
Arjun Arkal Rao |
| E-mail(s) |
arjunarkal.rao@ucsf.edu
|
| Organization name |
University of California, San Francisco
|
| Department |
CoLabs
|
| Lab |
Data Sciences CoLab
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| Street address |
505 Parnassus Ave, S-447
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| GSM6477010 |
Pooled GEX library for 8 lung organoids_1 |
| GSM6477011 |
Pooled LMO library for 8 lung organoids_1 |
| GSM6477012 |
Pooled GEX library for 8 lung organoids_2 |
| GSM6477013 |
Pooled LMO library for 8 lung organoids_2 |
|
| Relations |
| BioProject |
PRJNA870911 |
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