GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE248773 Query DataSets for GSE248773
Status Public on Dec 02, 2023
Title COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary SARS-CoV-2 infection can cause persistent respiratory sequelae, as seen in long COVID. However, the underlying mechanisms remain unclear. To investigate pulmonary cellular and transcriptomic changes mediated by SARS-CoV-2 and influenza infection, we characterized the SARS-CoV-2-infected K18-hACE2 (K18) mice and compared their lung recovery with a mouse-adapted influenza model and verified the finding in SARS-CoV-2-infected nonhuman primates and in fatal human COVID-19 cases. K18-hACE2 mice infected with a sub-lethal dose of SARS-CoV-2 lost body weight from 1 - 8 days post-infection (DPI), and then gradually returned to baseline weight between 8 -13 DPI. Infected mice showed patchy pneumonia associated with histiocytic inflammation, collagen deposition, and increased pulmonary interferon and inflammatory response signature gene changes at 21 and 45 DPI. Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. They also showed reduced activation of epithelial-to-mesenchymal transition and apical junction pathways compared to influenza (Flu)-infected mice. Histologically, influenza- but not SARS-CoV-2- infected mice showed extensive Krt5+ “pods” structure co-stained with stem cell markers Trp63/ NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ “pods” and proliferative stem cells were not observed in SARS-CoV-2 infection in the lungs of humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung which may underlie the persistent clinical symptoms of long COVID.
Overall design Comparative gene expression profiling analysis of RNA-seq data for COVID mice at 4DPI, 6DPI and 21DPI and Influenza infected mice.
Contributor(s) Wang C, Shamima Khatun M, Zhang Z, Allen MJ, Chen Z, Ellsworth CR, Currey JM, Dai G, Tian D, Bach K, Yin X, Traina-Dorge V, Rappaport J, Maness NJ, Blair RV, Kolls JK, Pociask DA, Qin X
Citation(s) 38092883
Submission date Nov 28, 2023
Last update date Jan 02, 2024
Contact name Jay Kolls
Organization name Tulane University
Department Medicine
Lab Center for Translational Research in Infection and Inflammation
Street address 1430 Tulane Ave
City New Orleans
State/province LA
ZIP/Postal code 70112
Country USA
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (21)
GSM7919722 K18-hACE2, SARS-CoV-2, Day21_1_bulk RNA
GSM7919723 K18-hACE2, SARS-CoV-2, Day21_2_bulk RNA
GSM7919724 K18-hACE2, SARS-CoV-2, Day21_3_bulk RNA
This SubSeries is part of SuperSeries:
GSE248778 COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes
BioProject PRJNA1045984

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE248773_CoV_K18_21dpi_Vs.CoV_K18_4dpi.csv.gz 54.6 Kb (ftp)(http) CSV
GSE248773_Flu_K18_4dpi_Vs.CoV_K18_4dpi.csv.gz 234.9 Kb (ftp)(http) CSV
GSE248773_Flu_K18_4dpi_vs_CoV_K18_4dpi_Naive.csv.gz 553.3 Kb (ftp)(http) CSV
GSE248773_Flu_K18_6dpi_Vs.CoV_K18_6dpi.csv.gz 205.4 Kb (ftp)(http) CSV
GSE248773_Flu_K18_6dpi_vs_CoV_K18_6dpi_Naive.csv.gz 719.3 Kb (ftp)(http) CSV
GSE248773_K18_CoV_21dpi_vs_K18_Naive.csv.gz 51.8 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap