Ontology highlight
ABSTRACT:
PROVIDER: PRJNA907958 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22513100.fastq.gz | Fastqsanger.gz | |||
| SRR22513200.fastq.gz | Fastqsanger.gz | |||
| SRR22513300.fastq.gz | Fastqsanger.gz | |||
| SRR22513400.fastq.gz | Fastqsanger.gz | |||
| SRR22513500.fastq.gz | Fastqsanger.gz |
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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.
2025-03-07 | MODEL2502180001 | BioModels
Project description:The mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CP remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the temporal remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We found that Mesp1 acts as a pioneer transcription factor (TF) and identified Zic TFs as essential cofactors that regulate Mesp1 pioneer activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
2022-05-18 | GSE165102 | GEO
Project description:The mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CP remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the temporal remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We found that Mesp1 acts as a pioneer transcription factor (TF) and identified Zic TFs as essential cofactors that regulate Mesp1 pioneer activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
2022-05-18 | GSE165101 | GEO
Project description:Mouse heart development arises fromMesp1 expressing cardiovascular progenitors that are specified at the early stage of gastrulation. Lineage tracing and clonal analysisof Mesp1 progenitors revealed that heart development arises from distinct populations of Mesp1+ cardiovascular progenitors (CPs) expressing Mesp1 at different time points during gastrulation that contribute to different heart regions and different cardiovascular lineages. However, it remains unclear what are the molecular mechanisms that control the early regional and lineage segregation of Mesp1 CPs. Here, we performedsingle cell RNA-sequencing of FACS isolated Mesp1 CPs in WT and Mesp1 null embryos at different times to define the cellular and molecular heterogeneity of the Mesp1CPs, identify the role of Mesp1 in regulating cellular heterogeneity and uncover the mechanisms associated with lineage and regional segregation during the early stages of gastrulation.We showed that Mesp1 CPs isolated at E6.75 and E7.25 are molecularly distinct and make the continuum betweenepiblast and later mesodermal cells including hematopoietic progenitors. Single cell transcriptome of Mesp1 deficient CPsshowed that Mesp1 is required for the exitof thepluripotent state and the induction of the cardiovascular gene expression program in vivo.Using dimensional reduction analysis, we identified distinct populations of Mesp1 CPs that correspond to progenitors committed to different celllineages and regions of the heart, identifying the molecular features associated with the early lineage and regional segregation. Notch1CREER lineage tracing, a marker preferentially expressed by one of the different Mesp1CP subpopulations, during the early stage of gastrulation marked almost exclusively ECs, demonstrating theexistence of an early Mesp1 subpopulation committed to the EC fate.This study uncoversthe cellular and molecular heterogeneity associated with early lineage restriction and regional segregation of the heart at the early stage of gastrulation.
2018-01-28 | GSE100471 | GEO
Project description:Cardiac development arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during the early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Altogether, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occurs very early during gastrulation. We used microarrays to characterize the molecular mechanisms that control Mesp1 progenitor specification and lineage segregation during the early stage of cardiac mesoderm formation, 50 Mesp1 H2B-GFP+ or Mesp1 H2B-GFP- cells at E6.5 or E7.5 from mouse embryos were sorted for RNA extraction, amplification and hybridization on Affimetrix microarrays. Microaarrays were performed on Mouse Genome 430 PM strip Affymetrix array. The overall design was repeated in two different biological samples.
2014-07-10 | E-GEOD-59033 | biostudies-arrayexpress
Project description:The mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CP remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the temporal remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We found that Mesp1 acts as a pioneer transcription factor (TF) and identified Zic TFs as essential cofactors that regulate Mesp1 pioneer activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
2022-05-18 | GSE165103 | GEO
Project description:The purpose of this study was to identify the source of Wnt signals that lead to development/proliferation of the heart fields, particularly the second heart field. To this end, we knocked out Wntless (Wls), which is necessary for Wnt secretion, in Mesp1+ lineage cells. We performed single cell RNA-seq to better identify the source of Wnt signals and the effects of the loss of Wnt secretion in mesoderm.
2021-01-23 | GSE165300 | GEO
Project description:Heart development is controlled by a complex transcriptional network composed of transcription factors and epigenetic regulators. Mutations in key developmental transcription factor MESP1, and chromatin factors such as PRC1 and cohesin components have been found in human congenital heart diseases (CHDs), although, their functional mechanism during heart development remains elusive. Here we find MESP1 interacts with RING1A/RING1, the core component of PRC1. RING1A depletion impairs human cardiomyocyte differentiation, and similar cardiac abnormalities were observed in Ring1A knockout mice as in patients with MESP1 mutations. Mechanistically, MESP1 associates with RING1A to activate cardiogenic genes through promoter-enhancer interactions mediated by cohesin and CTCF, and histone acetylation mediated by p300. Importantly, CHD mutations of MESP1 significantly affect such mechanisms and impair target gene activation. Together, our results demonstrate the importance of MESP1-RING1A complex in heart development and provide insights into pathogenic mechanisms of CHDs caused by mutations in MESP1, PRC1 and cohesin components.
2022-10-17 | GSE188721 | GEO
Project description:Cardiac development arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during the early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Altogether, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occurs very early during gastrulation. We used microarrays to characterize the molecular mechanisms that control Mesp1 progenitor specification and lineage segregation during the early stage of cardiac mesoderm formation,
2014-07-10 | GSE59033 | GEO