Biology subjects

Jahnsen, F. L.

Publications and source records attributed to Jahnsen, F. L..

12 recordsLinked to original sources

bioRxiv2025

The glutamine transporter Slc38a1 is widely expressed in the embryonic neurogenic niches and impacts neuronal volume, survival, and morphology

The amino acid glutamine, and its derivatives glutamate and GABA, are pivotal for neurogenesis. However, how glutamine is mechanistically supplied to the cells in the neurogenic niches and its broader impact on neurodevelopment, remain poorly characterized. The Solute carrier family 38 member 1 (Slc38a1) exhibits high affinity for glutamine and accumulates glutamine in select cells. We investigated whether Slc38a1 is essential for neurogenesis and whether it has an impact on brain structure and function. Slc38a1 mRNA transcript and protein are widely expressed in the embryonic brain, including in the dorsal pallium and sub-pallium. At embryonic day 15.5, Slc38a1 localizes in neuronal stem cells in the ventricular zone in the forebrain, while it localizes in mature neurons in the sub-ventricular zone of the hindbrain. In the adult brain, Slc38a1 is not detected in neuronal stem cells in the sub-granular zone, however, it is highly enriched in mature local parvalbumin+ and somatostatin+ interneurons and ependyma. Analyses of single-cell RNA sequencing data further reveal that both the number of Slc38a1-expressing cells and the average transcript level of Slc38a1 are significantly higher in embryo brain cells compared to adults. In the embryo, Slc38a1 transcripts are particularly enriched in immature neuronal lineages and embryonic oligodendrocyte precursor populations, whereas in the adult, expression is more prominent in neural progenitor cells and radial glia. Disruption of Slc38a1 in mice impacts body weight, brain size and glutamatergic neuronal volume, while dendritic arborization is diminished and cellular life span is shortened. Altogether, Slc38a1 is essential for normal neurodevelopment, indirectly regulates adult neurogenesis in the sub-granular zone and influence neuronal morphology and cell viability.

neuroscience↗

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↗

bioRxiv2024

Bin2cell reconstructs cells from high resolution Visium HD data

SummaryVisium HD by 10X Genomics is the first commercially available platform capable of capturing full scale transcriptomic data paired with a reference morphology image from archived FFPE blocks at sub-cellular resolution. However, aggregation of capture regions to single cells poses challenges. Bin2cell reconstructs cells from the highest resolution data (2 m bins) by leveraging morphology image segmentation and gene expression information. It is compatible with established Python single cell and spatial transcriptomics software, and operates efficiently in a matter of minutes without requiring a GPU. We demonstrate improvements in downstream analysis when using the reconstructed cells over default 8 m bins on mouse brain and human colorectal cancer data. Availability and ImplementationBin2cell is available at https://github.com/Teichlab/bin2cell, along with documentation and usage examples, and can be installed from pip. Probe design functionality is available at https://github.com/Teichlab/gene2probe Contactny1@sanger.ac.uk, st9@sanger.ac.uk Supplementary informationSupplementary data are available online.

bioinformatics↗

bioRxiv2023

Separate Gut Plasma Cell Populations Produce Autoantibodies Against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extraintestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are autoantibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have autoantibodies reactive with both transglutaminase enzymes. We here report that in DH both gut plasma cells and serum autoantibodies are specific for either TG2 or TG3 with no TG2-TG3 cross-reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, we define three conformational epitope groups. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, our results demonstrate parallel induction of anti-TG2 and anti-TG3 autoantibody responses involving separate B-cell populations in DH patients.

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↗

bioRxiv2021

Spatiotemporal single cell transcriptomic analyzis of human gut macrophages revealsmultiple functional and niche-specific subsets

Macrophages are a heterogeneous population of cells involved in tissue homeostasis, inflammation and cancer. Although macrophages are densely distributed throughout the human intestine, our understanding of how gut macrophages maintain tissue homeostasis is limited. Here we show that colonic lamina propria (LpM) and muscularis macrophages (MM) consist of monocyte-like cells that differentiate into multiple transcriptionally distinct subsets. LpM comprise subsets with proinflammatory properties and subsets high antigen presenting and phagocytic capacity. The latter are strategically positioned close to the surface epithelium. Most MM differentiate along two trajectories; one that upregulates genes associated with immune activation and angiogenesis, whereas the other upregulates genes associated with neuronal homeostasis. Importantly, MM are located adjacent to neurons and vessels. Cell-cell interaction and gene network analysis indicated that survival, migration, transcriptional reprogramming, and niche-specific localization of LpM and MM are controlled by an extensive interaction with tissue-resident cells and a few key transcription factors.

immunology↗

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↗

bioRxiv2018

Characterization of the endocrine pancreas in Type 1 Diabetes: islet size is maintained but islet number is markedly reduced

Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of specific beta-cell loss. Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size if the beta cells are not replaced by other cells or tissue. The number of islets per pancreas volume (islet density) would not be affected.\n\nIn this study, we compared the islet density, size, and size distribution in subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. Results show that subjects with T1D, regardless of disease duration, had a dramatically reduced islet number per mm2, while the islet size was similar in all groups. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that frequently had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally expressed in beta cells.\n\nBased on our findings, we propose that failure during childhood to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls.

pathology↗