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| Status |
Public on Jun 17, 2024 |
| Title |
Primary nasal viral infection rewires the tissue-scale memory response |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission, but the cellular composition at homeostasis, during infection, and during a memory response are poorly understood. Here, we generated a single-cell RNA-sequencing (scRNA-seq) atlas of the murine nasal mucosa sampling three distinct regions before and during primary and secondary influenza A virus (IAV) infection. Primary infection was largely restricted to respiratory mucosa and induced stepwise changes in immune and epithelial cell type, subset, and state composition over time. Following viral clearance (14 dpi), rare, previously undescribed Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells expressing multiple genes with immune communication potential increased concurrently with tissue-resident memory T (TRM)-like cells and early IgG+/IgA+ plasmablasts. Proportionality analysis coupled with cell-cell communication inference, alongside validation by in situ microscopy, underscored the CXCL16–CXCR6 signaling axis between MDMs and effector CD8 T cells 8dpi and KNIIFE cells and TRM cells 14 dpi. Secondary influenza challenge with a homologous or heterologous strain administered 60 dpi induced an accelerated and coordinated myeloid and lymphoid response without epithelial proliferation, illustrating how tissue-scale memory to natural infection engages both myeloid and lymphoid cells to reduce epithelial regenerative burden. Raw and processed single-cell counts matrices can be accessed and downloaded from the Broad Institute Single-Cell Portal from studies SCP2216 and SCP 2221.
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| Overall design |
6-8 week old C57BL/6 mice were innoculated with 10^4 plaque forming units of influenza A virus PR8 (H1N1) in the upper respiratory tract through intranasal instilation (5 µl/nostril). Three mice per time point were sacrificed and respiratory mucosa (RM), olfactory mucosa (OM), and lateral nasal gland (LNG) were harvested. Single-cell RNA-sequencing was performed using 10x Genomics 3' v3.1 transcriptomics kit with mouse replicates (per tissue region) combined together and labeled with antibody-barcoded "hashes" to differentiate between samples (using Biolegend TotalSeqB). For rechallenge and memory experiments, PR8 infected mice were rechallenged with the same dose of PR8 or 10^5 plaque forming units of X31 (H3N2) and only RM tissue was collected and processed.
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ADT/HTO barcode sequence hashtagged samples
TotalSeq-B0301 anti-mouse Hashtag 1 ACCCACCAGTAAGAC mouse 1, all samples
TotalSeq-B0302 anti-mouse Hashtag 2 GGTCGAGAGCATTCA mouse 2, all samples
TotalSeq-B0303 anti-mouse Hashtag 3 CTTGCCGCATGTCAT mouse 3, all samples
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| Contributor(s) |
Kazer SW, Match CM, von Andrian UH, Ordovas-Montanes J |
| Citation(s) |
38964332 |
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| Submission date |
May 02, 2024 |
| Last update date |
Sep 16, 2024 |
| Contact name |
Jose Ordovas-Montanes |
| E-mail(s) |
jose.ordovas-montanes@childrens.harvard.edu
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| Organization name |
Boston Children's Hospital
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| Department |
Gastroenterology, Hepatology and Nutrition Research
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| Street address |
300 Longwood Ave
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL30172 |
NextSeq 2000 (Mus musculus) |
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| Samples (42)
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| GSM8247657 |
Respiratory mucosa, naive, gene expression |
| GSM8247658 |
Respiratory mucosa, naive, hashtag oligo |
| GSM8247659 |
Olfactory mucosa, naive, gene expression |
| GSM8247660 |
Olfactory mucosa, naive, hashtag oligo |
| GSM8247661 |
Lateral nasal gland, naive, gene expression |
| GSM8247662 |
Lateral nasal gland, naive, hashtag oligo |
| GSM8247663 |
Respiratory mucosa, IAV, 2dpi, gene expression |
| GSM8247664 |
Respiratory mucosa, IAV, 2dpi, hashtag oligo |
| GSM8247665 |
Olfactory mucosa, IAV, 2dpi, gene expression |
| GSM8247666 |
Olfactory mucosa, IAV, 2dpi, hashtag oligo |
| GSM8247667 |
Lateral nasal gland, IAV, 2dpi, gene expression |
| GSM8247668 |
Lateral nasal gland, IAV, 2dpi, hashtag oligo |
| GSM8247669 |
Respiratory mucosa, IAV, 5dpi, gene expression |
| GSM8247670 |
Respiratory mucosa, IAV, 5dpi, hashtag oligo |
| GSM8247671 |
Olfactory mucosa, IAV, 5dpi, gene expression |
| GSM8247672 |
Olfactory mucosa, IAV, 5dpi, hashtag oligo |
| GSM8247673 |
Lateral nasal gland, IAV, 5dpi, gene expression |
| GSM8247674 |
Lateral nasal gland, IAV, 5dpi, hashtag oligo |
| GSM8247675 |
Respiratory mucosa, IAV, 8dpi, gene expression |
| GSM8247676 |
Respiratory mucosa, IAV, 8dpi, hashtag oligo |
| GSM8247677 |
Olfactory mucosa, IAV, 8dpi, gene expression |
| GSM8247678 |
Olfactory mucosa, IAV, 8dpi, hashtag oligo |
| GSM8247679 |
Lateral nasal gland, IAV, 8dpi, gene expression |
| GSM8247680 |
Lateral nasal gland, IAV, 8dpi, hashtag oligo |
| GSM8247681 |
Respiratory mucosa, IAV, 14dpi, gene expression |
| GSM8247682 |
Respiratory mucosa, IAV, 14dpi, hashtag oligo |
| GSM8247683 |
Olfactory mucosa, IAV, 14dpi, gene expression |
| GSM8247684 |
Olfactory mucosa, IAV, 14dpi, hashtag oligo |
| GSM8247685 |
Lateral nasal gland, IAV, 14dpi, gene expression |
| GSM8247686 |
Lateral nasal gland, IAV, 14dpi, hashtag oligo |
| GSM8247687 |
Respiratory mucosa, IAV, 60dpi, bio rep1, gene expression |
| GSM8247688 |
Respiratory mucosa, IAV, 60dpi, bio rep1, hashtag oligo |
| GSM8247689 |
Respiratory mucosa, IAV PR8 rechallenge, 2dprc, gene expression |
| GSM8247690 |
Respiratory mucosa, IAV PR8 rechallenge, 2dprc, hashtag oligo |
| GSM8247691 |
Respiratory mucosa, IAV PR8 rechallenge, 5dprc, gene expression |
| GSM8247692 |
Respiratory mucosa, IAV PR8 rechallenge, 5dprc, hashtag oligo |
| GSM8247693 |
Respiratory mucosa, IAV, 60dpi, bio rep2, gene expression |
| GSM8247694 |
Respiratory mucosa, IAV, 60dpi, bio rep2, hashtag oligo |
| GSM8247695 |
Respiratory mucosa, IAV X31 rechallenge, 2dprc, gene expression |
| GSM8247696 |
Respiratory mucosa, IAV X31 rechallenge, 2dprc, hashtag oligo |
| GSM8247697 |
Respiratory mucosa, IAV X31 rechallenge, 5dprc, gene expression |
| GSM8247698 |
Respiratory mucosa, IAV X31 rechallenge, 5dprc, hashtag oligo |
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| Relations |
| BioProject |
PRJNA1107234 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE266469_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of CSV, H5) |
| GSE266469_feature_barcodes.csv.gz |
97 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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