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Series GSE185006 Query DataSets for GSE185006
Status Public on Dec 16, 2021
Title Arginine methyltransferase regulates monocyte extravasation and function
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process underlying a variety of innate inflammatory responses across multiple organ systems, which requires rapid responses via post translational modifications (PTM) of proteins. Specifically, methylation of protein by arginine methyltransferases (PRMTs) is an epigenetic PTM implicated in inflammatory responses. However, how methyltransferases drive immune regulation particularly in the lung, the resultant tissue injury and whether this might be of therapeutic value has remained unclear. Here, we demonstrate that PRMT7 was increased in the lung of chronic obstructive pulmonary disease (COPD) patients and positively correlated with tissue injury. Accordingly, in clinically relevant models of COPD, lung fibrosis and skin injury, mice with reduced expression of PRMT7 were protected against disease development, due to decreased recruitment of pro-inflammatory monocytes to the site of injury. Mechanistically, we discovered in monocytes activation of NF-κB/RelA induces PRMT7, promoting mono-methylation of histones, which crucially regulates RAP1A and subsequent adhesion and migration ability. Furthermore, in pro-inflammatory monocytes, ALOX5 derived LTB4 induced ACSL4 expression in lung epithelial cells and consequently sensitized towards ferroptosis, thus aggravating tissue injury. Conclusively, specific targeting of arginine mono-methylation offers yet-unappreciated therapeutic potential against monocyte-driven inflammatory conditions.
 
Overall design Single-cell transcriptomics experiment after prolonged cigarette smoke exposure
 
Contributor(s) Conlon TM, Günsel GG, Jeridi A, Lang NJ, Ansari M, Strunz M, Angelidis I, Schiller HB, Yildirim A
Citation(s) 35031603
Submission date Sep 29, 2021
Last update date Feb 02, 2022
Contact name Meshal Ansari
Organization name Boehringer Ingelheim
Street address Birkendorfer Straße 65
City Biberach
ZIP/Postal code 88397
Country Germany
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (16)
GSM5603061 SMK-2m-2
GSM5603062 SMK-2m-3
GSM5603063 SMK-2m-4
Relations
BioProject PRJNA767361
SRA SRP339294

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
GSE185006_MonocyteExtravasation.h5ad.gz 6.9 Gb (ftp)(http) H5AD
GSE185006_MonocyteExtravasation_MNPs.h5ad.gz 613.6 Mb (ftp)(http) H5AD
GSE185006_MonocyteExtravasation_MonoMacro.h5ad.gz 288.8 Mb (ftp)(http) H5AD
GSE185006_MonocyteExtravasation_barcodes.txt.gz 328.3 Kb (ftp)(http) TXT
GSE185006_MonocyteExtravasation_cells_metadata.txt.gz 1.8 Mb (ftp)(http) TXT
GSE185006_MonocyteExtravasation_genes.txt.gz 76.8 Kb (ftp)(http) TXT
GSE185006_MonocyteExtravasation_raw_counts.mtx.gz 186.5 Mb (ftp)(http) MTX
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Raw data are available in SRA
Processed data are available on Series record

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