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| Status |
Public on Jul 26, 2022 |
| Title |
Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.
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| Overall design |
Examination of 2 sets of human choroid plexus brain organoids at week 4 and week 8, and cortical brain organoids at week 8 of in vitro culture
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| Contributor(s) |
Shaker MR, Wolvetang EJ |
| Citation missing |
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| Submission date |
Jul 19, 2022 |
| Last update date |
Jul 26, 2022 |
| Contact name |
Mohammed R Shaker |
| Organization name |
The University of Queensland
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| Department |
AIBN
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| Lab |
Stem cell engineering Lab
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| Street address |
Building 75,Cnr College Rd & Cooper Rd,, Brisbane
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| City |
St Lucia |
| State/province |
QLD |
| ZIP/Postal code |
4072 |
| Country |
Australia |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA860166 |
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