Tongue immune compartment analysis reveals spatial macrophage heterogeneity
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PROVIDER: PRJNA844014 | ENA |
REPOSITORIES: ENA
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Project description:Tongue immune compartment analysis reveals spatial macrophage heterogeneity [bulk RNA-Seq]
| PRJNA844024 | ENA
Project description:Tongue immune compartment analysis reveals spatial macrophage heterogeneity [bulk RNA-Seq]
| PRJNA844023 | ENA
Project description:The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication and articulation. As a barrier organ, which is constantly exposed to environmental pathogens,the tongue isexpected to host animmune cell network ensuringlocal immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here we characterised the tissue-resident immune compartment of the murine tongue during development, health anddisease, combining single cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae.Folr2+ macrophages were detected in deeper muscular tissue. The two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPSin vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.
2022-06-29 | GSE205158 | GEO
Project description:The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication and articulation. As a barrier organ, which is constantly exposed to environmental pathogens,the tongue isexpected to host animmune cell network ensuringlocal immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here we characterised the tissue-resident immune compartment of the murine tongue during development, health anddisease, combining single cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae.Folr2+ macrophages were detected in deeper muscular tissue. The two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPSin vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.
2022-06-29 | GSE205157 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-29 | GSE205162 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity. This intratumoral co-existence of classical and basal-like programs is evident in multi-scale transcriptomic and spatial analyses of resected, advanced-stage and chemotherapy-treated specimens and reciprocally linked to a diverse stromal immune microenvironment as well as worse clinical outcome. However, the underlying mechanisms of intratumoral subtype heterogeneity remain largely unclear. Here, by combining preclinical models, multi-center clinical, bulk and compartment-specific transcriptomic, proteomic, and bioimaging data from human specimens, we identified an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic CD68+ macrophages as a driver of intratumoral subtype co-existence along with an immunosuppressive tumor microenvironment with T cell exclusion. Our ATAC , ChIP-, and RNA-seq analyses revealed that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory immune signatures in tumor cells, antagonizing cJUN/AP1 signaling to favor a therapy-responsive classical neoplastic identity. Through the tumor microenvironment, this dichotomous regulation was further amplified via regional macrophage populations. Moreover, CD68+/TNF-α+ cells associated with a reactive phenotype and reduced CD8+ T cell infiltration in human PDAC tumors. Consequently, combined anti-TNF-α immunotherapy and chemotherapy resulted in reduced macrophage counts and promoted CD3+/CD8+ T cell infiltration in basal-like PDAC, leading to improved survival in preclinical murine models. We conclude that tumor cell intrinsic epigenetic programs, together with extrinsic microenvironmental cues, facilitate intratumoral subtype heterogeneity and disease progression.
2023-12-31 | GSE245941 | GEO
Project description:Spatial proteogenomics reveals distinct and evolutionarily-conserved hepatic macrophage niches (spatial)
| PRJNA793008 | ENA
Project description:About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient matched liver metastases.
2023-02-17 | PXD039409 | Pride
Project description:Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about the spatial intratumor heterogeneity (ITH) and the temporal clonal evolutionary processes in this cancer. Interestingly, the epigenetic profiling also showed strong evidence of spatial ITH, and the phyloepigenetic trees were extremely similar with the phylogenetic ones, indicating the interplay and co-dependency of genetic and epigenetic alterations in ESCC. We found that several genes were both mutated and hypermethylated at their promoters, such as ASXL1 and EPHA7. Our integrated investigations of the spatial ITH and the temporal clonal evolution might provide insights into developing biomarkers for early diagnosis of ESCC, as well as personalized therapeutic targets for treating this malignancy. DNA methylation profiles of 12 tumor regions and 2 matched normal esophageal epithelial tissues from three M-WES-examined ESCC cases (ESCC01, ESCC03 and ESCC05) were performed using Illumina Infinium HumanMethylation450K platform (Illumina, San Diego, CA) at the Epigenome Center of University of Southern California.
2016-08-20 | E-GEOD-79366 | biostudies-arrayexpress
Project description:The concept of macrophage niches has redefined the classification of macrophages, moving beyond ontogeny and function to encompass the mutually beneficial loop of signals in a given tissue environment. As such, tissue-resident macrophages adapt to local environmental signals within and between tissues to acquire specific functional adaptations. Neoplastic transition transforms the tissue environment, which then raises the question as to how existing macrophage subsets and their niche contribute to the tumor-associated macrophage (TAM) compartment. By combining single cell RNA sequencing and 2-photon imaging, we discovered that considerable TAM heterogeneity in mammary breast tumor is driven by niches that exist prior to tumor development, macrophage localization within the tumor and the stage of tumor malignancy. The differentiation of TAM subsets was associated with distinct signaling paths, homing and transcription factor signatures. We find similar functional heterogeneity in human breast TAMs. In overview, we show that specific niches within the tumor rather than defined activation states (e.g. the M1/M2 dichotomy) are the major drivers of TAM plasticity and heterogeneity. The distinctions created by this analysis show how treatments of different tumor indications should propose targeting specific TAMs at this niche/pathway level.
2022-05-05 | GSE184096 | GEO