GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306630/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306630GEOGSEfalseInterplay of Pro-coagulatory and Neutrophil-derived Anti-coagulatory proteins in C1q-NET driven blood coagulationNeutrophils 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.2026/08/27GSE306630GSM9204933GSM9204944GSM9204943GSM9204942GSM9204952GSM9204941GSM9204937GSM9204948GSM9204947GSM9204936GSM9204946GSM9204935GSM9204934GSM9204945GSM9204940GSM9204951GSM9204950GSM9204939GSM9204949GSM920493816791306630Homo sapiens