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Series GSE193782 Query DataSets for GSE193782
Status Public on Apr 19, 2022
Title ScRNA-seq Expression of APOC2 and IFI27 Identifies Four Alveolar Macrophage Superclusters in Cystic Fibrosis and Healthy BALF
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Alveolar macrophages (AMs) reside on the luminal surface of the airways and alveoli, ensuring proper gas exchange by ingesting cellular debris and pathogens, and regulating inflammatory responses. Therefore, understanding the heterogeneity and diverse roles played by AMs, interstitial macrophages, and recruited monocytes is critical for treating airway diseases. We performed single-cell RNA sequencing on 113,213 bronchoalveolar lavage cells from four healthy and three uninflamed cystic fibrosis subjects and identified two MARCKS+LGMN+IMs, FOLR2+SELENOP+ and SPP1+PLA2G7+ IMs, monocyte subtypes, DC1, DC2, migDCs, plasmacytoid DCs, lymphocytes, epithelial cells, and four AM superclusters (families) based on the gene expression of IFI27 and APOC2 These four AM families have at least eight distinct functional members (subclusters) named after their differentially expressed gene(s): IGF1, CCL18, CXCL5, cholesterol, chemokine, metallothionein, interferon, and small-cluster AMs. Interestingly, the chemokine cluster further divides with each subcluster selectively expressing a unique combination of chemokines. One of the most striking observations, besides the heterogeneity, is the conservation of AM family members in relatively equal ratio across all AM superclusters and individuals. Transcriptional data and TotalSeq technology were used to investigate cell surface markers that distinguish resident AMs from recruited monocytes. Last, other AM datasets were projected onto our dataset. Similar AM superclusters and functional subclusters were observed, along with a significant increase in chemokine and IFN AM subclusters in individuals infected with COVID-19. Overall, functional specializations of the AM subclusters suggest that there are highly regulated AM niches with defined programming states, highlighting a clear division of labor.
Overall design We performed single-cell RNA sequencing (scRNA-seq) on 113,213 BAL cells from four healthy donors and three CF subjects. Transcriptional data and TotalSeq technology were used to confirm cell surface markers that distinguish resident AMs from recruited monocytes.
Web link
Contributor(s) Li X, Kolling FW, Aridgides D, Mellinger D, Ashare A, Jakubzick CV
Citation(s) 35820705
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 HL115334 Understanding the unique role endogenous APC subtypes play during the rejection of MAg-mismatched cells DARTMOUTH COLLEGE Claudia V Jakubzick
R01 HL135001 Functional roles of human pulmonary DC's in the lung draining lymph nodes DARTMOUTH COLLEGE Claudia V Jakubzick
R35 HL155458 Human and mouse transcriptome profiling identifies cross-species homology of mononuclear phagocytes DARTMOUTH COLLEGE Claudia V Jakubzick
P30 CA023108 Cancer Center Support Grant DARTMOUTH COLLEGE Steven D Leach
P20 GM130454 Center for Quantitative Biology: A focus on "omics", from organisms to single cells DARTMOUTH COLLEGE MICHAEL L WHITFIELD
S10 OD025235 10X Genomics Chromium Single-cell Sequencing to Expand Research At Dartmouth DARTMOUTH COLLEGE CRAIG R TOMLINSON
Submission date Jan 17, 2022
Last update date Jul 20, 2022
Contact name Claudia V Jakubzick
Phone 6036462234
Organization name Dartmouth College
Department Microbiology and Immunology
Lab Jakubzick
Street address 1 Medical Center Drive, Rm 626 W Borwell, PO#1250960
City Lebanon
State/province NH
ZIP/Postal code 03756
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (14)
GSM5821038 Healthy Control 1 mRNA
GSM5821039 Healthy Control 1 Protein
GSM5821040 Healthy Control 2 mRNA
BioProject PRJNA797951

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Supplementary file Size Download File type/resource
GSE193782_Meta.Data.txt.gz 7.5 Mb (ftp)(http) TXT
GSE193782_SeuratObject.rds.gz 17.3 Gb (ftp)(http) RDS
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