Expression profiling of mouse primary prostate cells from WT mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE92622 | GEO | 2019/09/02
REPOSITORIES: GEO
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Project description:In the normal prostate, most basal and some luminal cells are castration-resistant (CR). The identity of these CR cells and their relation to CR prostate cancer are unresolved. We compared single-cell expression profiles of prostate cells sorted from hormonally naïve (HN) and castrated mice. We found both basal and luminal-localized cells, particularly the latter, were molecularly heterogeneous. CR luminal cells and a subset of HN luminal cells exhibited a similar “intermediate” expression pattern, including high-level expression of multiple prostate stem/progenitor marker genes and androgen receptor gene. We validated LY6D as a marker linking CR luminal cells to luminal progenitors. LY6D+ prostate cells, including LY6D+ luminal cells, were enriched for organoid-forming potential regardless of the presence or absence of androgen. Krt8-based lineage-tracing revealed that LY6D+ CR luminal cells produced LY6D- normal luminal cells upon regeneration, but LY6D+ luminal cancer cells under PTEN-deficiency. Furthermore, prostate cancers originating from CR luminal cells (LY6D+) exhibited a more advanced phenotype than those from HN luminal cells (LY6D+ or LY6D-). Lastly, LY6D amplification/upregulation appear associated with advanced prostate cancer in patient samples. Together, our studies demonstrate LY6D as a novel progenitor marker predictive of lethal CR disease.
2018-12-21 | GSE92473 | GEO
Project description:By using luminal lineage tracing model, here we report the regulatory network underlying intrinsically castration-resistant LY6D+ luminal progenitors during prostate tumourigenesis. The luminal cell-specific PTEN deficient mouse model of PCa (K8-CreERT2;PtenFlox/Flox;R26-StopFlox/Flox-EYFP (K8PY) and the control K8-CreERT2;R26-StopFlox/Flox-EYFP (K8Y) mice) are used in this study.
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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.
2015-04-30 | GSE67070 | GEO
Project description:Androgen deprivation is the mainstay of therapy for progressive prostate cancer. Despite initial and dramatic tumor inhibition, most men eventually fail therapy and die of metastatic castration-resistant (CR) disease. Here, we characterize the profound degree of genomic alteration found in CR tumors using array CGH, gene expression arrays, and FISH. By cluster analysis, we show that the similarity of the genomic profiles from primary and metastatic tumors is driven by the patient. Using data adjusted for this similarity, we identify numerous high-frequency alterations in the CR tumors, such as 8p loss and chromosome 7 and 8q gain. By integrating array CGH and expression array data, we reveal genes whose correlated values suggest they are relevant to prostate cancer biology. We find alterations that are significantly associated with the metastases of specific organ sites, and others with CR tumors versus the tumors of patients with localized prostate cancer, not treated with androgen deprivation. Within the high-frequency sites of loss in CR metastases, we find an over-representation of genes involved in cellular lipid metabolism, including PTEN. Finally, using FISH we verify the presence of a gene fusion between TMPRSS2 and ERG suggested by chromosome-21 deletions detected by array CGH. We find the fusion in 54% of our CR tumors, and 81% of the fusion-positive tumors contain cells with multiple copies of the fusion. Our investigation lays the foundation for a better understanding of and possible therapeutic targets for CR disease, the poorly responsive and final stage of prostate cancer.
2009-09-29 | GSE18259 | GEO
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.
2015-04-30 | E-GEOD-67070 | biostudies-arrayexpress
Project description:Androgen deprivation is the mainstay of therapy for progressive prostate cancer. Despite initial and dramatic tumor inhibition, most men eventually fail therapy and die of metastatic castration-resistant (CR) disease. Here, we characterize the profound degree of genomic alteration found in CR tumors using array CGH, gene expression arrays, and FISH. By cluster analysis, we show that the similarity of the genomic profiles from primary and metastatic tumors is driven by the patient. Using data adjusted for this similarity, we identify numerous high-frequency alterations in the CR tumors, such as 8p loss and chromosome 7 and 8q gain. By integrating array CGH and expression array data, we reveal genes whose correlated values suggest they are relevant to prostate cancer biology. We find alterations that are significantly associated with the metastases of specific organ sites, and others with CR tumors versus the tumors of patients with localized prostate cancer, not treated with androgen deprivation. Within the high-frequency sites of loss in CR metastases, we find an over-representation of genes involved in cellular lipid metabolism, including PTEN. Finally, using FISH we verify the presence of a gene fusion between TMPRSS2 and ERG suggested by chromosome-21 deletions detected by array CGH. We find the fusion in 54% of our CR tumors, and 81% of the fusion-positive tumors contain cells with multiple copies of the fusion. Our investigation lays the foundation for a better understanding of and possible therapeutic targets for CR disease, the poorly responsive and final stage of prostate cancer. The aim of this study was to characterize the genomic changes identified in a set of matched castrate-resistant primary and metastatic prostate cancers. Tumor cells were isolated by laser-capture microdissection from 14 patients, a total of 54 tumor samples. LCM capture samples were isolated from multiple metastastases from all but one patient from whom a single metastasis was available. Primary prostate tumor samples were collected from 12 patients. DNA was amplified by either ligation-mediated PCR (LMP) or WGA (Sigma-Aldrich, St. Louis, MO, USA). Reference DNA was isolated from peripheral blood from a single female individual.
2010-05-22 | E-GEOD-18259 | biostudies-arrayexpress
Project description:Single-cell RNA-sequencing has emerged as a powerful technology to assess heterogeneity within defined cell populations. Here, we comprehensively study the heterogeneity of a previously described B220+CD117intCD19-NK1.1- uncommitted hematopoietic progenitor with combined lymphoid and myeloid potential (EPLM). Using staining for surface markers together with functional assays, we describe four subpopulations of this progenitor with distinct lineage developmental potentials. Amongst them, the Ly6D+SiglecH-CD11c- fraction was lymphoid restricted exhibiting strong B-cell potential, whereas the Ly6D-SiglecH-CD11c- fraction showed mixed lympho-myeloid potential. Single-cell RNA-sequencing of these subsets revealed that the latter population is composed of a mixture of cells with distinct lymphoid and myeloid genetic signatures and identified a subgroup as the potential precursor of Ly6D+SiglecH-CD11c-. We observed a B-cell priming gradient within the Ly6D+SiglecH-CD11c- subset and propose a herein newly identified subgroup as the direct precursor of the first B-cell committed stage. Our study demonstrates that the multipotency of B220+CD117intCD19-NK1.1- progenitors is a result of underlying heterogeneity at the single-cell level. Moreover, it highlights the validity of single-cell transcriptomics to resolve cellular heterogeneity and identify developmental relationships in hematopoietic progenitors.
2017-10-11 | GSE102455 | GEO
Project description:Methods: To characterize the prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. Results: We identify a population of tumor-associated club cells that could be associated with prostate carcinogenesis and uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer. ERG- tumor cells, compared to ERG+ cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids recapitulate tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Conclusions:Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.
2021-08-23 | GSE176031 | GEO