Spatial transcriptomics reveals unexpected histological heterogeneity in primary prostate
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PROVIDER: PRJNA1028117 | ENA |
REPOSITORIES: ENA
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Project description:Heterogeneity at different dimensions is a hallmark of prostate cancer (PCa). To carefully dissect the cellular and molecular landscape of PCa with distinct phenotypes, we conducted spatial transcriptomics (ST) and parallel single-nucleus RNA sequencing (snRNA-seq) technologies to identify areas of vulnerability amenable to therapeutic intervention. We here report the identification of an androgen receptor positive (AR+) but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small-cell carcinoma (SCLPC). snRNA-seq was performed on two samples representative of adenocarcinoma and SCLPC phenotypes, respectively. Further molecular characterization and wet experiments prioritized protein translation, represented by upregulation of many ribosomal proteins (RPs), and SP1, a transcriptional factor that drive SCLPC phenotype, as two potential therapeutic targets for treating AR-independent CRPC. Altogether, our studies reveal the non-rare existence of SCLPC in admixed PCa pathology, which may serve as a cell-of-origin for CRPC, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.
2024-01-27 | GSE245388 | GEO
Project description:Histological heterogeneity in primary prostate
| PRJNA1028110 | ENA
Project description:Intratumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
| EGAS00001003001 | EGA
Project description:Tissue and organ function has been conventionally understood in terms of the interactions among discrete and homogeneous cell types. This approach has proven difficult in neuroscience due to the marked diversity across different neuron classes, but may also be further hampered by prominent within-class variability. Here, we considered a well-defined, canonical neuronal population â hippocampal CA1 pyramidal cells â and systematically examined the extent and spatial rules of transcriptional heterogeneity. Using next-generation RNA sequencing, we identified striking variability in CA1 PCs, such that the differences along the dorsal-ventral axis rivaled differences across distinct pyramidal neuron classes. This variability emerged from a spectrum of continuous expression gradients, producing a profile consistent with a multifarious continuum of cells. This work reveals an unexpected amount of variability within a canonical and narrowly defined neuronal population and suggests that continuous, within-class heterogeneity may be an important feature of neural circuits. Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
2016-01-05 | E-GEOD-67403 | biostudies-arrayexpress
Project description:BackgroundPatients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy.MethodsWe included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP).ResultsUsing DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region.ConclusionsThese findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells.
| S-EPMC10844893 | biostudies-literature
Project description:Spatial Transcriptome Assays Reveals Gliomas Heterogeneity
| PRJNA1126248 | ENA
Project description:Spatial transcriptomics was performed on human hepatoblastomas to determine features associated with histologic heterogeneity.
2024-09-12 | GSE249965 | GEO
Project description:These data were used in the spatial transcriptomics analysis of the article titled \\"Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging\\".
2024-04-22 | E-MTAB-13991 | biostudies-arrayexpress
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