Project description:Kilian2024 - Immune cell dynamics in Cue-Induced Extended Human Colitis Model
Single-cell technologies such as scRNA-seq and flow cytometry provide critical insights into immune cell behavior in inflammatory bowel disease (IBD). However, integrating these datasets into computational models for dynamic analysis remains challenging. Here, Kilian et al., (2024) developed a deterministic ODE-based model that incorporates these technologies to study immune cell population changes in murine colitis. The model parameters were optimized to fit experimental data, ensuring an accurate representation of immune cell behavior over time. It was then validated by comparing simulations with experimental data using Pearson’s correlation and further tested on independent datasets to confirm its robustness. Additionally, the model was applied to clinical bulk RNA-seq data from human IBD patients, providing valuable insights into immune system dynamics and potential therapeutic strategies.
Figure 4c, obtained from the simulation of human colitis model is highlighted here.
This model is described in the article:
Kilian, C., Ulrich, H., Zouboulis, V.A. et al. Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. npj Syst Biol Appl 10, 69 (2024). https://doi.org/10.1038/s41540-024-00395-9
Abstract:
Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.
This model was curated during the Hackathon hosted by BioMed X GmbH in 2024.
Project description:We performed a detailed and precise characterisation of the clonally expanded leukemic cells in CD8+ T-cell Large Granular Lymphocytic Leukemia (T-LGLL). By combining scRNA+TCRαβ-seq with bulk RNA sequencing data we showed evidence of a strong antigen-driven immune response that shapes the entire immune cell repertoire in T-LGLL. Our study highlights how the whole immune cell repertoire including the hyperexpanded CD8+ T-LGLL cells, the non-leukemic CD8+ cells, CD4+ cells, and monocytes contribute to the CD8+ T-LGLL disease phenotype. The raw data for this study have been deposited to the controlled-access archive EGA under EGAS00001005297.
Project description:This dataset contains processed single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) collected from six hepatocellular carcinoma (HCC) patients, before and after curative therapy. Samples were profiled using the 10x Genomics Chromium platform. The dataset includes gene expression matrices and associated metadata for 12 samples (6 pre-therapy, 6 post-therapy). These data support the analysis of peripheral immune cell dynamics in response to tumor removal
Project description:In this study, we investigated somatic mutations in T cells in patients with various hematological disorders. To analyze immune cell phenotypes with somatic mutations, we performed scRNA+TCRab sequencing from 9 patients with chronic GVHD and clonal expansions of CD4+ or CD8+ T cells based on T cell receptor sequencing. CD45+ PBMCs (lymphocytes and monocytes) were sorted with BD Influx cell sorter and subjected to sequencing with Chromium VDJ and Gene Expression platform (v1.1, 10X Genomics). Sequencing was performed with Novaseq 6000 (Illumina). The immune cell phenotypes were compared to healthy controls processed in the same laboratory (accession number E-MTAB-11170). Due to data privacy concerns, the raw sequencing data is in the European Genome-Phenome Archive (EGA) under accession code [xxxx] and can be requested through the EGA Data Access Committee.
Project description:This study investigates the immune characteristics of tissue-resident memory T cells in the human fallopian tube in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) and paired T-cell receptor sequencing (scTCR-seq) were performed on samples from non-cancerous fallopian tube tissue, metastatic omental tumors, and peripheral blood from HGSOC patients. The dataset enables analysis of tissue-resident T cell populations, clonal relationships across tissues, and immune features associated with tumor progression. These data provide a resource for studying tissue-resident T cell heterogeneity, clonal expansion, and tumor-associated immune responses in ovarian cancer.
Project description:Hypothalamic nuclei which regulate homeostatic functions express leptin receptor (LepR), the primary target of the satiety hormone leptin. Single-cell RNA sequencing (scRNA-seq) has facilitated the discovery of a variety of hypothalamic cell types. However, low abundance of LepR transcripts prevented further characterization of LepR cells. Therefore, we perform scRNA-seq on isolated LepR cells and identify eight neuronal clusters, including three uncharacterized Trh-expressing populations as well as 17 non-neuronal populations including tanycytes, oligodendrocytes and endothelial cells. This includes food restriction to measure the response of Lepr positive cells to fasting. Using FACS sorting into 384 well plates and Celseq2 method, we generated a high-quality dataset containing a median of 12,082 unique counts and 4,756 genes per cell.
Project description:Single-cell RNA-seq (scRNA-seq) on nocodazole and DMSO treated cells before and after differentiation into endoderm. hPSC colonies were treated with DMSO or 100ng/ml nocodazole for 16 hours and induced to differentiate into definitive endoderm for three days. Single cells were subsequently collected in either undifferentiated conditions (Und) or after 3 days of endoderm differentiation (Endoderm) and then sorted onto 384 well plates for Smart-Seq2 processing.
Project description:The goal of this project was to analyze gene expression changes and gene expression heterogeneity at the single cell level upon DNA damage induced by ionizing radiation (IR). To this end, human U-2 OS cells were left untreated or exposed to 4 Gy of IR. 48 h after IR exposure, single cells were sorted into 384 well plates for scRNA-seq analysis.
Project description:<p>Over 135 million births occur each year; yet, the molecular underpinnings of human parturition in gestational tissues, and in particular the placenta, are still poorly understood. The placenta is a complex heterogeneous organ including cells of both maternal and fetal origin, and insults that disrupt the maternal-fetal dialogue could result in adverse pregnancy outcomes such as preterm birth. There is limited knowledge of the cell type composition and transcriptional activity of the placenta and its compartments during physiologic and pathologic parturition. To fill this knowledge gap, we used scRNA-seq to profile the placental villous tree, basal plate, and chorioamniotic membranes of women with or without labor at term and those with preterm labor. </p>
Project description:The study investigates the interaction between rAAV and the innate immune system. We conducted single cell RNA-sequencing (scRNA-seq) of PBMCs from six healthy human donors, comparing samples taken either before or after 1, 4 or 24 hrs of incubation with rAAV8. As a control, scRNA-seq was performed on untreated whole blood incubated under the same culture conditions to consider the potential impact of the ex vivo culture on the blood cells.