Expression data from human pancreatic ductal adenocarcinomas by stroma types
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157353 | GEO | 2020/09/03
REPOSITORIES: GEO
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Project description:This study sought the basis for the failure of immunosurveillance in pancreatic ductal adenocarcinoma (PDA). The FAP+ cell was shown to be immunosuppressive in a spontaneous PDA model. Bioinformatic analyses show it to be identical to the Carcinoma-associated fibroblast (CAF). FAP+ cells were sorted from pancreatic ductal adenocarcinoma. Cells were isolated in duplicate experiments and these were analysed separately. These were compared separately to previously published publicly available CD4+ T-cell subset data (C57BL/6 mice and Foxp3-RFP mice (Line 8374) GEO accession GSE20898), and previously published FAP+ cell datasets (transgenic albino (Tyr-/-) C57BL/6 mouse, GEO accession GSE39438).
2012-11-30 | E-GEOD-42605 | biostudies-arrayexpress
Project description:Purpose Cancer-associated fibroblasts (CAFs) are a key component of tumors. We aimed to profile the proteome of cancer cell lines representing three common cancer types (lung, colorectal and pancreatic) and a representative CAF cell line from each tumor type to gain insight into CAF function and identify new CAF biomarkers. Experimental Design We used isobaric labeling, liquid chromatography and mass spectrometry to evaluate the proteome of 9 cancer and 3 CAF cell lines. Functions of selected differentially expressed proteins in CAF cell lines were further investigated using siRNA and the expression levels of candidate novel CAF biomarkers were evaluated by immunohistochemistry in 30 human tumor specimens. Results Of the 9460 proteins evaluated, functional enrichment analysis revealed N-glycan biosynthesis and extracellular membrane proteins to be upregulated in CAFs and not in cancer cells. 85 proteins had 16-fold higher expression in CAFs compared to cancer cells. These included previously known CAF markers like ACTA2, FAP and SDC2. Novel biomarkers overexpressed in CAFs were noted, including HSPB6 and PTGS1. SiRNA knockdown of these genes encoding these proteins did not reduce contractility in lung CAFs, suggesting they were not crucial to this function despite high expression. Immunohistochemical analysis of 30 tumor samples (10 lung, 10 colorectal and 10 pancreatic) showed HSPB6 and PTGS1 expression were restricted to the stroma. Conclusions An unbiased analysis of the differences in the proteome of cancer cells compared to CAFs revealed increased expression of HSPB6 and PTGS1 in CAFs.
2023-08-21 | PXD040360 | Pride
Project description:Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute the human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover subTMEs, histologically definable tissue states anchored in fibroblast plasticity, with regional relationships to tumor immunity, subtypes, differentiation, and treatment response. Reactive subTMEs rich in complex but functionally coordinated fibroblast communities were immune-hot and inhabited by aggressive tumor cell phenotypes. The matrix-rich deserted subTMEs harbored less activated fibroblasts and tumor- suppressive features yet were markedly chemoprotective and enriched upon chemotherapy. SubTMEs originated in fibroblast differentiation trajectories and transitory states were notable both in single cell transcriptomics and in situ. The intratumoral co-occurrence of subTMEs produced patient-specific phenotypic and computationally predictable heterogeneity tightly linked to malignant biology. Therefore, heterogeneity within the plentiful, notorious pancreatic TME is not random but marks fundamental tissue organizational units.
| EGAD00001008155 | EGA
Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
2024-01-16 | GSE228972 | GEO
Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
2024-01-16 | GSE228981 | GEO
Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
2024-01-16 | GSE228980 | GEO
Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
2024-01-16 | GSE228953 | GEO
Project description:Purpose: Use scRNA Seq to find stromal subpopulations and define how these subpopulations contribute to salivary gland proacinar differentiation. Method: scRNA Seq on stromal enriched cells from E16 salivary organoids. Model closely related cells using PCA and UMAP regressions. Find genes that broadly and specifically define cell subpopulations. Results: The stromal fibroblasts have multiple subpopulations. Stromal cells can be subdivided by their expression of Pdgfra, Pdgfrb, Thy1, and Acta2. Conclusions: Organoids grown with FGF2 selects for Pdgfra expressing stroma and without FGF2 Acta2 stroma dominates.
2022-03-01 | GSE193041 | GEO
Project description:Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant fraction of patients fails to respond. Recent studies to understand transcriptomic determinants of immunotherapy response have pinpointed stroma-mediated resistance mechanisms. To gain a better understanding of the stromal biology at the cellular and molecular levels in LUAD, we obtained the transcriptomes of 256,379 single cells with 13,857 mesenchymal cells from 9 treatment-naïve patients. Among the mesenchymal cells, we identify subsets of FAP+PDPN+ cancer-associated fibroblasts (CAFs) and ACTA2+MCAM+ pericytes, which enrich in tumors, differentiate from lung resident fibroblasts and possess a myofibroblast phenotype. By utilizing imaging-mass cytometry, we found that both subsets are topographically adjacent to the perivascular niche and have close spatial interaction with endothelial cells (ECs). Modelling of ligand and receptor interactomes between mesenchymal and ECs identifies that NOTCH3/NOTCH signaling drives the cell-cell interaction in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or tuning down NOTCH3 level in mesenchymal cells reduced collagen production and suppressed cell invasion. By evaluating the clinical relevance of NOTCH signaling using bulk-RNA sequencing data, we demonstrate that NOTCH3 correlates with poor survival in stroma-rich patients and that a T-cell inflammation gene signature predicts survival only in low-NOTCH3 expressing patients. Our study underscores the importance of NOTCH3 in regulating tumor stroma biology and may serve as a potential target for immunotherapy combination strategies.
2024-01-31 | GSE253013 | GEO
Project description:FAP+ cells had been reported to be present only in healing wounds and at sites of tissue remodelling. We have found FAP+ cells in many normal tissues and aimed to investigate whether these cells were related or whether FAP is upregulated in response to an external stimulus on a variety of cells. Furthermore we wanted to investigate whether FAP+ cells are simply fibroblasts and so compared their transcriptomic profiles to that of a typical fibroblastic population, the murine embryonic fibroblast. FAP+ cells were sorted from two mesenchymal tissues, visceral adipose and skeletal muscle, and from an epithelial organ, the pancreas. These were compared to MEFs. Cells were isolated in duplicate experiments and these were analysed separately. These were compared to previously published publically available CD4+ T-cell subset data.
2013-07-15 | E-GEOD-39438 | biostudies-arrayexpress