{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306630/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306630"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Interplay of Pro-coagulatory and Neutrophil-derived Anti-coagulatory proteins in C1q-NET driven blood coagulation","description":"Neutrophils interact with the external milieu in both tissue and blood microenvironments and are emerging as important regulators of blood coagulation 1-3. In this study, we explored whether complement induces Neutrophil Extracellular Trap (NET) formation and related blood coagulation using human donor-derived neutrophils. Complement C1q induces NETosis in Lipopolysaccharide (LPS) O127 primed neutrophils, while LPS alone does not induce NETosis. Bulk RNA sequencing revealed a unique LPS-driven altered neutrophil state and complement sensitivity for NETosis was found to be transcriptionally- dependent. Using an arrayed CRISPR Knockout screen in the neutrophil-like differentiated HL60 cells (dHL60), we identified that SCARF1 and Complement Receptor 3 are required for C1q-NETosis. Since NETs contain pro- coagulatory components such as DNA and histones, we investigated whether C1q-related NETs influenced blood coagulation. LPS+ C1q NETs were associated with reduced coagulation activity compared to LPS treatment alone. We further found that LPS upregulated Tissue Factor expression and coagulation-related activity in neutrophils. Furthermore, neutrophils secrete anticoagulant proteins, including Protein C and Tissue Factor Pathway Inhibitors, during C1q- mediated NET formation that functionally regulates NET-related coagulation. C1q- NETs also activate the coagulation factors FXII and FXI, facilitating both intrinsic coagulation and kallikrein-dependent bradykinin production. This study elucidates how NETs regulate both pro- coagulatory and anti-coagulatory components that may influence pathophysiology of disease.","dates":{"publication":"2026/08/27"},"accession":"GSE306630","cross_references":{"GSM":["GSM9204933","GSM9204944","GSM9204943","GSM9204942","GSM9204952","GSM9204941","GSM9204937","GSM9204948","GSM9204947","GSM9204936","GSM9204946","GSM9204935","GSM9204934","GSM9204945","GSM9204940","GSM9204951","GSM9204950","GSM9204939","GSM9204949","GSM9204938"],"GPL":["16791"],"GSE":["306630"],"taxon":["Homo sapiens"]}}