Tongue immune compartment analysis reveals spatial macrophage heterogeneity [bulk RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA844024 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19451852_1.fastq.gz | Fastqsanger.gz | |||
| SRR19451852_2.fastq.gz | Fastqsanger.gz | |||
| SRR19451853_1.fastq.gz | Fastqsanger.gz | |||
| SRR19451853_2.fastq.gz | Fastqsanger.gz | |||
| SRR19451854_1.fastq.gz | Fastqsanger.gz |
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Project description:Tongue immune compartment analysis reveals spatial macrophage heterogeneity [bulk RNA-Seq]
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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.
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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.
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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 is expected to host an immune cell network ensuring local 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 and disease, 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. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in 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.
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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.
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