Biology subjects

Baekkevold, E. S.

Publications and source records attributed to Baekkevold, E. S..

7 recordsLinked to original sources

bioRxiv2025

Easydecon: A Lightweight Workflow for Cell Type Analysis in High-Definition Spatial Transcriptomics Assays

The emergence of high-resolution spatial transcriptomics platforms, such as VisiumHD, has enabled transcriptome-wide spatial profiling at near-single-cell resolution. However, existing analysis tools often lack scalability or compatibility with this new resolution, limiting their utility for multimodal cell type analysis. We present Easydecon, a lightweight and modular computational framework for spatial transcriptomics analysis using marker genes from single-cell RNA sequencing datasets. Easydecon uses a two-phase strategy, which firstly detects expression hotspots and then refines cell type assignments with similarity-based methods. We demonstrate its efficacy by resolving cell type subsets with high accuracy. Easydecon supports integration with segmentation tools and outperforms established methods in speed, usability and cell type recovery.

bioinformatics↗

bioRxiv2025

Single cell spatial transcriptomics identifies coordinated cellular programs that are associated with good prognosis in microsatellite stable colorectal cancer

It has been reported that microsatellite instable (MSI) tumors in colorectal cancer (CRC) exhibit stronger anti-tumor responses than microsatellite stable (MSS) tumors. Analyzing scRNA-seq data from 185 CRC patients we found that immune, structural, and cancer cells in MSS tumors with high numbers of tumor-infiltrating CD8 T cells and macrophages (TAMs; CD8hiTAMhi) and CD8lowTAMhi tumors were enriched for pathways associated with anti- and pro-tumor responses, respectively. In CD8hiTAMhi tumors, TAMs expressed an IFN-induced phenotype (e.g. GBP1, CXCL9, IFITM3) and high infiltration of GBP1+ TAMs was associated with better overall survival (n=941). High-resolution spatial transcriptomics (Visium HD) revealed that GBP1+ TAMs clustered with CXCL13+IFNG+PDCD1+ CD8 T cells in tumoral niches, suggesting that GBP1+ TAMs were involved in recruitment and activation of tumor-reactive CD8 T cells. Together, we uncovered coordinated cellular programs across cell types in the microenvironment of MSS tumors, based on simple classification variables, that were strongly associated with prognosis.

cancer biology↗

bioRxiv2025

Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies

A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19- CD45- (age>20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19-CD45+ (age>10 years) and short-lived CD19+CD45+ (age<2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.

immunology↗

bioRxiv2023

cellsnake: a user-friendly tool for single cell RNA sequencing analysis

BackgroundSingle-cell RNA sequencing (scRNA-seq) provides high-resolution transcriptome data to understand the heterogeneity of cell populations at the single-cell level. The analysis of scRNA-seq data requires the utilization of numerous computational tools. However, non-expert users usually experience installation issues, a lack of critical functionality or batch analysis modes, and the steep learning curves of existing pipelines. ResultsWe have developed cellsnake, a comprehensive, reproducible, and accessible single-cell data analysis workflow, to overcome these problems. Cellsnake offers advanced features for standard users and facilitates downstream analyses in both R and Python environments. It is also designed for easy integration into existing workflows, allowing for rapid analyses of multiple samples. ConclusionAs an open-source tool, cellsnake is accessible through Bioconda, PyPi, Docker, and GitHub, making it a cost-effective and user-friendly option for researchers. By using cellsnake, researchers can streamline the analysis of scRNA-seq data and gain insights into the complex biology of single cells.

bioinformatics↗

bioRxiv2020

The human small intestine comprises two subsets of regulatory Foxp3+ CD4 T cells with very different life span and functional properties.

BackgroundRegulatory CD4 T cells (Tregs) in the mice gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Tregs in the human gut is limited. ObjectiveHere, we performed a detailed characterization of Foxp3+ CD4 Tregs in the human small intestine. MethodsTregs and conventional CD4 T cells derived from normal intestine as well as from transplanted duodenum and celiac disease lesions were subjected to extensive immunophenotyping and their suppressive activity and ability to produce cytokines were assessed. ResultsSmall intestinal Foxp3+ CD4 T cells were CD45RA- CD127- CTLA4+ and suppressed proliferation of autologous T cells. Approximately 60% of the Tregs expressed the transcription factor Helios. When stimulated, Helios- Tregs produced IL-17, IFN-{gamma} and IL-10, whereas Helios+ Tregs produced very low levels of these cytokines. By sampling mucosal tissue from transplanted human duodenum we demonstrated that donor Helios+ Tregs have a short life span whereas Helios- Tregs persisted for at least 1 year post-transplantation. In normal small intestine, Foxp3+ Tregs constituted only 2% of all CD4 T cells, while in active celiac disease both subsets expanded 5-10-fold. ConclusionThe small intestine contains two subsets of Tregs with different functional capacities and very different life span. Both subsets are scarce in the normal situation but increase dramatically in a chronic inflammatory setting.

immunology↗

bioRxiv2019

CD4+ T cells persist for years in the human small intestine and mediate robust Th1 immunity.

Studies in mice and humans have shown that CD8+ T cell immunosurveillance in non-lymphoid tissues is dominated by resident populations. Whether CD4+ T cells use the same strategies to survey peripheral tissues is less clear. Here, examining the turnover of CD4+ T cells in transplanted duodenum in humans, we demonstrate that the majority of CD4+ T cells were still donor-derived one year after transplantation. In contrast to memory CD4+ T cells in peripheral blood, intestinal CD4+ TRM cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4+ TRM cells were very potent cytokine producers; the vast majority being polyfunctional TH1 cells, whereas a minor fraction produced IL-17. Interestingly, a fraction of intestinal CD4+ T cells produced granzyme-B and perforin after activation. Together, we show that the intestinal CD4+ T-cell compartment is dominated by resident populations that survive for more than 1 year. This finding is of high relevance for the development of oral vaccines and therapies for diseases in the gut.

immunology↗

bioRxiv2019

Resident memory CD8 T cells persist for years in human small intestine

In human small intestine, most CD8 T cells in the lamina propria and epithelium express a resident memory (Trm) phenotype and persist for at least one year in transplanted tissue. Intestinal CD8 Trm cells have a clonally expanded immune repertoire that is stable over time and exhibit enhanced protective capabilities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/553792v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@10c19aaorg.highwire.dtl.DTLVardef@168e86forg.highwire.dtl.DTLVardef@73f0f5org.highwire.dtl.DTLVardef@1d08d10_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe vast majority of CD8 T cells in the human small intestine are Trm cells C_LIO_LICD8 Trm cells persist for >1 year in transplanted duodenum C_LIO_LIIntraepithelial and lamina propria CD8 Trm cells show highly similar TCR repertoire C_LIO_LIIntestinal CD8 Trm cells efficiently produce cytokines and cytotoxic mediators C_LI

immunology↗