Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA317775 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3351000.fastq.gz | Fastqsanger.gz | |||
| SRR3351001.fastq.gz | Fastqsanger.gz | |||
| SRR3350998.fastq.gz | Fastqsanger.gz | |||
| SRR3350999.fastq.gz | Fastqsanger.gz |
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Project description:The T-box transcription factor TBX18 is essential to mesenchymal cell differentiation in several tissues and Tbx18 loss-of-function results in dramatic organ malformations and perinatal lethality. Here we demonstrate for the first time that Tbx18 is required for the normal development of periductal smooth muscle stromal cells in prostate, particularly in the anterior lobe, with a clear impact on prostate health in adult mice. Prostate abnormalities are only subtly apparent in Tbx18 mutants at birth; to examine postnatal prostate development we utilized a relatively long-lived hypomorphic mutant and a novel conditional Tbx18 allele. Similar to the ureter, cells that fail to express Tbx18 do not condense normally into smooth muscle cells of the periductal prostatic stroma. However, in contrast to ureter, the periductal stromal cells in mutant prostate assume a hypertrophic, myofibroblastic state and the adjacent epithelium becomes grossly disorganized. To identify molecular events preceding the onset of this pathology, we compared gene expression in the urogenital sinus (UGS), from which the prostate develops, in Tbx18-null and wild type littermates at two embryonic stages. Genes that regulate cell proliferation, smooth muscle differentiation, prostate epithelium development, and inflammatory response were significantly dysregulated in the mutant urogenital sinus around the time that Tbx18 is first expressed in the wild type UGS, suggesting a direct role in regulating those genes. Together, these results argue that Tbx18 is essential to the differentiation and maintenance of the prostate periurethral mesenchyme and that it indirectly regulates epithelial differentiation through control of stromal-epithelial signaling.
2016-04-26 | GSE80083 | GEO
Project description:The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation.
2009-09-09 | GSE17906 | GEO
Project description:Inflammation has a causal role in many cancers. In prostate cancers, epidemiological data suggest a link between prostatitis and subsequent cancer development, but a proof for this concept in a tumor model has been lacking. A constitutively active version of the IkappaB kinase 2 (IKK2), the molecule activated by a plethora of inflammatory stimuli, was expressed specifically in the prostate epithelium. Signaling of the IKK2/NF-kappaB axis was insufficient for transformation of prostate tissue. However, while PTEN+/- epithelia exhibited intraepithelial neoplasias only recognizable by nuclear alterations, additional IKK2 activation led to an increase in tumor size and formation of cribriform structures and to a fiber increase in the fibroblastic stroma. This phenotype was coupled with inflammation in the prostate gland characterized by infiltration of granulocytes and macrophages. Molecular characterization of the tissues showed a specific loss of smooth muscle markers as well as expression of chemokines attracting immune cells. Isolation of epithelial and stromal cells showed differential chemokine expression by these cells. Correlation studies showed the inflammatory phenotype coupled to loss of smooth muscle in infiltrated glands, but maintenance of the phenotype in glands where inflammation had decreased. Despite the loss of the smooth muscle barrier, tumors were not invasive in a stable genetic background. Data mining revealed that smooth muscle markers are downregulated in human prostate cancers and literature data show that loss of these markers in primary tumors is associated with subsequent metastasis. Our data show that loss of smooth muscle and invasiveness of the tumor are not coupled. Thus, inflammation during early steps of tumorigenesis can lead to increased tumor size and a potential change in the subsequent metastatic potential, but the tumor requires an additional transformation to become a carcinoma. Microarray analysis was used to determine expression differences in lateral prostates from mice with PTEN+/- IKK2ca/ca epithelium (n=3) compared to lateral prostates from mice with PTEN+/- epithelium (n=3).
2011-07-01 | E-GEOD-26410 | biostudies-arrayexpress
Project description:To investigate proteins potentially involved in the survival of prostate epithelial cells, we initially collected prostate tissues from 32 BPH patients. Subsequently, we conducted immunohistochemistry (IHC) staining using an anti-alpha-smooth muscle actin (α-SMA) antibody, recognized as a marker for smooth muscle cells and myofibroblasts. We delineated the areas of the stroma, glandular epithelium, and glandular lumen based on this staining. We digitized and conducted subsequent analysis of the relative percentage of different tissue components, including the stroma/epithelium ratio (S/E). Specimens were ranked based on the S/E ratio, leading to the categorization of the 9 specimens with the lowest S/E into group 1 (Epithelium-hi), where the epithelial components may have more significant roles in BPH development. Conversely, the 9 specimens with the highest S/E were placed in group 2 (Epithelium-lo). Within each group, we further subdivided them into 3 subgroups labeled as A through E. Subsequently, we employed isobaric tags for relative and absolute quantitation (iTRAQ)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the differentially expressed proteins (DEPs) between the two main groups.
2024-01-24 | PXD048857 |
Project description:Inflammation has a causal role in many cancers. In prostate cancers, epidemiological data suggest a link between prostatitis and subsequent cancer development, but a proof for this concept in a tumor model has been lacking. A constitutively active version of the IkappaB kinase 2 (IKK2), the molecule activated by a plethora of inflammatory stimuli, was expressed specifically in the prostate epithelium. Signaling of the IKK2/NF-kappaB axis was insufficient for transformation of prostate tissue. However, while PTEN+/- epithelia exhibited intraepithelial neoplasias only recognizable by nuclear alterations, additional IKK2 activation led to an increase in tumor size and formation of cribriform structures and to a fiber increase in the fibroblastic stroma. This phenotype was coupled with inflammation in the prostate gland characterized by infiltration of granulocytes and macrophages. Molecular characterization of the tissues showed a specific loss of smooth muscle markers as well as expression of chemokines attracting immune cells. Isolation of epithelial and stromal cells showed differential chemokine expression by these cells. Correlation studies showed the inflammatory phenotype coupled to loss of smooth muscle in infiltrated glands, but maintenance of the phenotype in glands where inflammation had decreased. Despite the loss of the smooth muscle barrier, tumors were not invasive in a stable genetic background. Data mining revealed that smooth muscle markers are downregulated in human prostate cancers and literature data show that loss of these markers in primary tumors is associated with subsequent metastasis. Our data show that loss of smooth muscle and invasiveness of the tumor are not coupled. Thus, inflammation during early steps of tumorigenesis can lead to increased tumor size and a potential change in the subsequent metastatic potential, but the tumor requires an additional transformation to become a carcinoma.
2011-07-01 | GSE26410 | GEO
Project description:Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
2021-11-02 | PXD025770 | Pride
Project description:Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
2021-11-02 | PXD020561 | Pride
Project description:Organotypic in vitro culture is useful to model mammalian disease in numerous tissues. Normal epithelial differentiation and carcinogenesis both undergo in vivo regulation by stroma, but current culture methods exclude stroma. To mimic this in vivo environment, we developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells supported increased organoid formation and expressed growth factors and WNT-related genes involved in epithelial differentiation. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Tumoroids derived from primary prostate cancer maintained differential expression of the prostate cancer marker AMACR only in the presence of stroma. Stroma-induced phenotypes were similar in all patients examined, yet maintained inter-patient heterogeneity in the degree of response. Addition of stroma to in vitro organoid culture recapitulated the in vivo microenvironment by inducing organization of benign organoids into branching structures and preserving prostate cancer phenotypes.
2018-05-30 | GSE115052 | GEO
Project description:The aim of the study was to characterize the molecular mechanism involved in TGF-M-CM-^_ mediated smooth muscle formation in vitro. We employed rat bone marrow derived Oct4 expressing clones of multipotent adult progenitor cells (rMAPC). We subjected these cells to differentiation towards smooth muscle cell as previously reported using TGF-M-CM-^_1. The differentiation process reuires 6 days with media change every 2 days followed by RNA harvest. RNA was isolated using commercially available kits (Qiagen RNA easy micro kit). RNA integrity and quality was assessed prior to labeling and hybridization. As a control RNA from rat aortic smooth muscle cells was commercially obtained. Two biological replicate clones of rMAPC cells were used for the differentiation to smooth muscle like cells. The RNA was harvested at days 0, 2, 4 and 6 in triplicates. The RNA from primary smooth muscle cells was commercially obtained and was used in duplicates as control.
2012-10-09 | E-GEOD-32990 | biostudies-arrayexpress
Project description:The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation. Experiment Overall Design: A total of 15 arrays were run for the following sample types obtained from 10 patients: Experiment Overall Design: 2 CD90+ prostate tumor-associated stromal: Experiment Overall Design: Patient 1: CP_Str_08-028_CD90posi Experiment Overall Design: Patient 2: 08-032_CP_strom_CD90posi Experiment Overall Design: 2 CD13+ normal bladder stromal: Experiment Overall Design: Patient 3: 06-125_NB_CD13posi Experiment Overall Design: Patient 4: 06-070_NB_str_CD13posi Experiment Overall Design: 1 CD13+ bladder tumor-associated stromal: Experiment Overall Design: Patient 5: 07-008_CB_str_CD13posi Experiment Overall Design: 5 whole tissue prostate cancer and 5 normal tissue from matched pairs: Experiment Overall Design: Patient 6: 05-206_CaP, 05-206_NP Experiment Overall Design: Patient 7: 05-213_CaP, 05-213_NP Experiment Overall Design: Patient 8: 05-214_CaP, 05-214_NP Experiment Overall Design: Patient 9: 05-218_CaP, 05-218_NP Experiment Overall Design: Patient 10: 05-220_CaP, 05-220_NP Experiment Overall Design: Additionally, 8 arrays were run for the following sample types obtained from 7 patients: Experiment Overall Design: 5 CD49a+ normal prostate stromal (PMID 16638148): Experiment Overall Design: Patient 1: CD49a_01-26-04 Experiment Overall Design: Patient 2: CD49a_03-23-04 Experiment Overall Design: Patient 3: CD49a_03-04-04 Experiment Overall Design: Patient 4: CD49a-1_06-02-04 Experiment Overall Design: Patient 5: CD49a-4_06-02-04 Experiment Overall Design: 3 CD26+ prostate cancer (2 biological replicates, 1 sample run twice): Experiment Overall Design: Patient 6: 05-179_CD26t Experiment Overall Design: Patient 6: 05-179_CD26t_2 Experiment Overall Design: Patient 7: 08-032_CP_epi_CD26posi Experiment Overall Design: The following two prostate cancer samples were also included in the analyses: Experiment Overall Design: CD26+ cancer cell, replicate 1 Experiment Overall Design: CD26+ cancer cell, replicate 2 Experiment Overall Design: The tissue samples consisted of prostate tissue specimens obtained from patients undergoing radical prostatectomy under approval by the University of Washington Institutional Review Board. The same approach was used for both cancer-free and cancer-enriched (where at least 85% of the cells in the corresponding frozen section were of cancer) samples. To obtain bladder stromal cells for analysis, tissue specimens were obtained from cystoprostatectomy surgeries. For cell sorting, the collected specimens were processed within hours. Cell types were sorted using monoclonal antibodies specific for tumor-associated prostate stromal cells (CD90), tumor-associated bladder stromal cells (CD13) and normal bladder stromal cells (CD13) with MACS.
2009-09-18 | E-GEOD-17906 | biostudies-arrayexpress