Spatial transcriptomics reveals unexpected histological heterogeneity in primary prostate
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1028117 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26385016.fastq.gz | Fastqsanger.gz | |||
| SRR26385017.fastq.gz | Fastqsanger.gz | |||
| SRR26385018.fastq.gz | Fastqsanger.gz | |||
| SRR26385019.fastq.gz | Fastqsanger.gz | |||
| SRR26385020.fastq.gz | Fastqsanger.gz |
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Project description:Histological heterogeneity in primary prostate
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Project description:This project introduces a spatial multi-omics (SMOx) pipeline integrating MALDI-2 mass spectrometry imaging (MSI) with Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) to investigate molecular heterogeneity in human prostate cancer (PCa). MALDI-2 MSI was used to map lipid distributions with enhanced sensitivity compared to conventional MALDI, enabling detailed visualization of metabolic alterations across tissue regions. Through non-rigid co-registration via H&E images and Gaussian-weighted granularity matching, MSI data were spatially aligned with transcriptomic and histological layers. This integration revealed lipidgene expression relationships associated with distinct cell populations and pathological states within heterogeneous prostate tissues. The resulting dataset provides a high-resolution molecular atlas of PCa, demonstrating the power of MSI-driven spatial multi-omics to uncover lipid-based signatures that refine tissue annotation and support molecular pathology studies.
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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
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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.
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