Genome-wide chromatin occupancy of MIR205HG/LEADR in prostate basal epithelial cells
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ABSTRACT:
PROVIDER: PRJNA832237 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18923400.fastq.gz | Fastqsanger.gz | |||
| SRR18923401.fastq.gz | Fastqsanger.gz | |||
| SRR18923402.fastq.gz | Fastqsanger.gz | |||
| SRR18923399.fastq.gz | Fastqsanger.gz |
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Project description:Aside serving as host gene for the microRNA miR-205, MIR205HG transcribes for a nuclear chromatin-associated long noncoding RNA (lncRNA) able to restrain the differentiation of prostate basal cells, a finding that led to its reannotation as LEADR (Long Epithelial Alu-interacting Differentiation-related RNA). In our previous work (PMID: 30659180), we showed that genes that are modulated upon manipulation of MIR205HG/LEADR are characterized by the presence of an Alu sequence in their promoters. Notably, an Alu element also spans the first and second exon of MIR205HG/LEADR, thus suggesting its possible involvement in target selection and binding. Here, we performed Chromatin Isolation by RNA precipitation followed by DNA-sequencing (ChIRP-seq) to map MIR205HG/LEADR chromatin occupancy at a genome-wide level in prostate basal cells.
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Project description:The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome. Human total RNA profiles of 3 pairs of benign prostatic basal and luminal populations freshly purified from prostate tissues of three prostate cancer patients by deep RNA-seq.
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Project description:We used RNA-seq to compare the expression profiles of mouse prostate tumors originated from epithelial basal cells to those originated from luminal cells. We next generated expression signatures for both basal and luminal origin tumors by comparison of tumor samples to their respective controls. By comparing luminal to basal signatures we identified a prognostic molecular signature for prostate cancer patient survival. Pten was deleted in prostate basal or luminal cells to induce tumor formation and tumor expression profiles were analyzed by RNA-seq.
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Project description:We used RNA-seq to compare the expression profiles of mouse prostate tumors originated from epithelial basal cells to those originated from luminal cells. We next generated expression signatures for both basal and luminal origin tumors by comparison of tumor samples to their respective controls. By comparing luminal to basal signatures we identified a prognostic molecular signature for prostate cancer patient survival.
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Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq
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Project description:The prostate basal cell compartment is postulated to contain stem/progenitors due to its resistance to castration, capability to differentiation into basal, luminal and neuroendocrine cell lineages of prostate epithelium, and susceptibility to oncogenic transformation. However, the heterogeneity and the interrelationship among different cell subpopulations within prostate basal cells remain largely unknow. Here we find that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation. The Zeb1+ basal cells are resistant against androgen deprivation, possess greater efficiency to produce prostate spheroids in vitro, undergo self-renewal, and can generate functional prostate with all three cell lineages in vivo at the single cell level. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+ basal cell subset shares gene expression profile with both epithelial and mesenchymal cells and stands out uniquely among all the cell clusters. Pseudotemporal reconstruction revealed three cell lineage trajectories through which the Zeb1+ basal cell subset gives rise to differentiated basal cells, and androgen dependent or independent intermediate cells. at the starting point in the developmental trajectories of cell clusters in prostate basal epithelium. In addition, Zeb1 positive basal cells can be detected in human prostate samples. Our data demonstrate that these Zeb1+ cells are bona fide PSCs in the basal cell compartment. Identification of the prostate stem cell (PSC) and its differentiation path is crucial to advance our understanding of prostate development and tumorigenesis.
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