Hypertension remains a poorly understood condition, and the understanding of the sympathetic nervous systems role in this disease remains even more limited. In this study, RNA-sequencing is used to identify transcriptomal differences in the sympathetic stellate ganglia between the 16-week-old normotensive wistar strain and the spontaneously hypertensive rat strain.This dataset should allow for further molecular characterisation of hypertensive changes in a cardiac-innervating sympathetic ganglion. Overall design: Comparison of normotensive and hypertensive rat stellate ganglia. 4 biological replicates for both 16 week wistar and SHR stellate ganglia samples were contrasted
Neurotransmitter Switching Coupled to β-Adrenergic Signaling in Sympathetic Neurons in Prehypertensive States.
No sample metadata fields
View SamplesOral squamous cell carcinoma (OSCC) is a lethal disease and early death usually occurs as a result of local invasion and regional lymph node metastases. We used microarrays to identify down or upregulated genes in OSCCs compared with non-malignant controls.
Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation.
Disease, Disease stage, Cell line
View SamplesTranscriptome profiling of de novo-derived ccRCC cell cultures and their matching parental tumours. VHL-mutant and VHL wild-type cultures were established by isolating CA9+ and CA9- cells from tumor samples using FACS. Overall design: RNASeq expression profiling of 18 renal cell carcinoma samples, including 6 patient tumours, 6 VHL mutant and 6 VHL WT derivative cell cultures
Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine.
No sample metadata fields
View SamplesHost-environment interfaces such as the dermis comprise tissue macrophages as the most abundant resident immune cell type. Diverse tasks, i.e. to resist against invading pathogens, to attract bypassing immune cells from penetrating vessels and to aid tissue development and repair require a dynamic postnatal coordination of tissue macrophages specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into distinct subsets by adapting single cell transcriptomics, fate-mapping and tissue imaging. We thereby identified a small phenotypically and transcriptionally distinct subset of embryo-derived skin macrophages that was maintained and largely excluded from the overall postnatal exchange by monocytes. These macrophages specifically interacted with dermal sensory nerves, surveilled and trimmed the myelin sheets and regulated axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by step-wise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment. Overall design: Single Cell Sequencing was performed on CD45+CD11b+CD64+Lin-(lineage B220, CD3, NK1.1, Siglec-F, Ly6G) CX3CR1 (low, mid, high) macrophage subsets from mouse dermis after enzymatic digestion
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.
Age, Specimen part, Cell line, Subject
View SamplesMiR-1246 was found to promote tumorigenesis and metastasis in sevearl cancer types. In the context of tumor microenvironment, tumor-associated macrophages are a central part typically correlated with poor prognosis.
Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.
Specimen part
View SamplesCells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAM) are often associated with poor prognosis in cancer. In order to better understand the influence of tumor cell apoptosis and in particular its effect on TAM, we investigated global gene expression signatures of undisturbed TAM engaged in engulfment of apoptotic tumor cells. We studied a xenograft model of an aggressive starry-sky non-Hodgkins lymphoma, Burkitts lymphoma (BL), in which apoptotic tumor cells are common and frequently observed in association with the starry-sky TAM (SS-TAM, so called because they appear histologically as stars in a sky of tumor cells) that accumulate in these tumors. We used a BL cell line (BL2) whose cells phenotypically resemble the tumor biopsy cells from which the line was derived including the capacity to undergo apoptosis constitutively. BL xenografts in SCID mice closely recapitulated the starry-sky histological picture of the human lymphoma. Due to the high sensitivity of macrophages to their environments, we adopted laser-capture microdissection of individual SS-TAM in BL xenografts in order to obtain unbiased in situ transcriptional profiles of these cells, which we compared specifically with those of similarly-captured macrophages, the tingible-body macrophages from normal germinal centers (GCM). The rationale for this comparison was based upon BL being a germinal center malignancy and tingible-body macrophages being regarded as normal equivalents of SS-TAM.
Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
Sex, Specimen part
View SamplesAt present, medical treatments of synchronous and metachronous liver metastases from colorectal cancer are not differentiated. The aim of the study was to analyze the gene expression profiling of synchronous and metachronous lesions in order to identify molecular signatures as possible basis for choice of systemic therapies. Fresh tissues specimens from metastases of 18 patients undergone liver surgery were collected (10 synchronous and 8 metachronous lesions). Gene expression profiling was studied using Affymetrix platform. Two different profiles were identified. Pathway related to the Epidermal Growth Factor receptor (EGFr) was upregulated in metachronous lesions whereas pathways mainly related to inflammation in synchronous lesions. Real Time-PCR, Western Blotting and ELISA confirmed that the metachronous lesions had the overexpression of EGFr, but the synchronous ones had the overexpression of Cyclo-oxygenase 2 (COX-2). These results suggest that synchronous or metachronous liver metastases from colorectal cancer could be differently treated on the basis of different molecular pathways.
Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice.
Specimen part
View SamplesPrimary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD.
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
Specimen part
View SamplesHypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sex, Specimen part
View SamplesDeregulated activity of the LATS tumor suppressors has broad implications on cellular and tissue homeostasis. We examined the consequences of downregulation of either LATS1 or LATS2 in breast cancer. Consistent with their proposed tumor suppressive roles, expression of both paralogs is significantly downregulated in human breast cancer, and loss of either paralog accelerated mammary tumorigenesis in mice. However, each paralog had a distinct impact on breast cancer. Thus, LATS2 depletion in luminal B tumors resulted in metabolic rewiring, with increased glycolysis and reduced PPARg signaling. Furthermore, pharmacological activation of PPARg elicited LATS2-dependent death in luminal B-derived cells. In contrast, LATS1 depletion augmented cancer cell plasticity, skewing luminal B tumors towards increased expression of basal-like features, in association with increased resistance to hormone therapy. Hence, these two closely related paralogs play distinct roles in protection against breast cancer; tumors with reduced expression of either LATS1 or LATS2 may rewire signaling networks differently and thus respond differently to anti-cancer treatments. Overall design: RNA was isolated from Lats1-CKO and Lats2-CKO PyMT tumors (4 samples from each). For each genotype, the corresponding wt littermate controls were used (3 samples in each batch).
LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state.
Specimen part, Subject
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