Siakaeva, E. | Search bioRxiv

bioRxiv2026

CITE-seq of murine bone marrow plasmacytoid dendritic cells and haematopoietic progenitor cells in sepsis

This dataset contains single-cell transcriptomic and surface protein profiles of bone marrow cells enriched for plasmacytoid dendritic cells (pDCs) and haematopoietic progenitor populations from septic and sham-operated mice. Sepsis was induced in BALB/c wild-type mice using cecal ligation and puncture (CLP) of moderate severity, with sham surgery as control. Bone marrow was collected 36 hours after surgery, depleted for selected lineage-positive cells by fluorescence-activated cell sorting, and processed using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq). Sample demultiplexing was performed using hashtag oligonucleotides. The dataset includes gene expression matrices, antibody-derived tag counts, and barcode assignments for 13,725 cells, with a comparable distribution of sham and CLP samples across the total cell number. It may be used to study transcriptional states, surface marker expression, and phenotypic diversity of bone marrow cells in sepsis, to compare with other immunological and haematological single-cell datasets, or to train and benchmark computational tools for multimodal single-cell data analysis.

immunology↗

bioRxiv2025

Serpins A1/A3 within tumor-derived extracellular vesicles support pro-tumoral bias of neutrophils in cancer

Neutrophils are known to play an important regulatory role during tumor progression in several types of cancer. However, the mechanisms responsible for their tumorigenic bias and extended lifespan in cancer are not clear to date. This study uncovers a previously unknown mechanism by which tumor-derived small extracellular vesicles (sEVs), via their serpin cargo, reprogram neutrophils to adopt a tumor-supporting phenotype. We demonstrated here an elevated content of plasma sEVs during head and neck cancer progression, and their significant cargo enrichment with inhibitors of neutrophil serine proteases: serpins A1 and A3. Mechanistically, neutrophils educated with serpin-rich tumor-derived sEVs displayed typical pro-tumoral characteristics, including prolonged lifespan and activated CD62Llow CD11bhigh PDL1high phenotype. Functionally, such neutrophils demonstrated a strong ability to promote the epithelial-to-mesenchymal transition of tumor cells. Moreover, such neutrophils induced remarkable suppression of cytotoxic CD8 T cells, significantly reducing their tumor cell-killing capacity. Importantly, serpin cargo was essential for this activity, as serpin-depleted sEVs failed to reprogram neutrophils. These findings again highlight the clinical significance of sEVs and suggest their serpin content as important mediators of pro-tumoral functionality. Targeting the biogenesis or uptake of such immunosuppressive sEVs, or modifying their cargo, could potentially serve as a potent adjuvant anti-cancer therapy.

cancer biology↗