Single cell hierarchy of the mouse vaginal epithelium
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE142212 | GEO | 2019/12/18
REPOSITORIES: GEO
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Project description:Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in the pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. We here uncovered CSRNP1 as a key driver on collagen degradation in human-derived vaginal fibroblasts. Apoptosis of POP patient-derived vaginal fibroblasts was suppressed after knocking down CSRNP1. Silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. In line with this, CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal subject-derived vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis showed that differentially expressed genes affected by CSRNP1 overexpression in normal vaginal fibroblasts were mainly enriched in the Wnt signaling pathway, which was crucial for the onset and progression of POP. Silencing of CSRNP1 upregulated the expression of nuclear β-catenin and induced nuclear translocation of β-catenin in H2O2-induced normal vaginal fibroblast. Furthermore, collagen deposition caused by CSRNP1 knockdown was curbed after treatment with a Wnt pathway inhibitor DKK1. Our study indicates that the CSRNP1 may be involved in POP progression through the Wnt signaling, which provides a potential therapeutic strategy for POP.
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Project description:Single cell hierarchy of the mouse vaginal epithelium
| PRJNA596227 | ENA
Project description:Wnt signals control three functions of intestinal crypts: maintenance of Lgr5 stem cells, proliferation of transit-amplifying daughters and formation of Paneth cells. Here, we study how the Wnt effector β-catenin/Tcf4 cooperates with the Wnt-activated transcription factor Ascl2 to control a stem cell transcription program. DNA elements that are co-occupied and synergistically regulated by Ascl2 and Tcf4 specifically map to stem cell genes. In vitro, Tcf4-/- mini-guts are rescued by Ascl2 expression, while Ascl2-/- organoids are rescued by Wnt signaling. A direct auto-activatory loop leads to an on/off expression pattern of Ascl2 with a threshold that depends on the previous state. Wnt/R-spondin1 activates this loop. This mechanism interprets Wnt levels in crypts and translates this continuous signal into a discrete Ascl2 âonâ or âoffâ decision. In turn Ascl2, together with β-catenin/Tcf, activates stem cell genes. Thus, Ascl2 forms a transcriptional 'stemness switch' that is both Wnt-responsive and Wnt-dependent Examination of Tcf4, B-catenin and Ascl2 DNA occupancy in murine intestinal organoids and human colorectal cancer cell lines *** Original raw files unavailable due to loss during backup ***
2016-07-15 | E-GEOD-84456 | biostudies-arrayexpress
Project description:Background: Vaginal birth causes injury to the pelvic floor and may lead to urinary incontinence. Cell therapy has been proposed to assist in functional recovery. Objective: To assess if intra-arterial injection of mesoangioblasts (MABs) or Vascular Endothelial Growth Factor (VEGF)-overexpressed MABs, improves urethral and vaginal function recovery after simulated vaginal delivery (SVD). Results: All stem-cell injected rats had external urethral sphincteric and vaginal function recovery within 14d, as compared to half of controls. Functional recovery was paralleled by improved muscle regeneration and microvascularization. Recovery was not different between autologous and allogenic MABs. MABsallo-VEGF accelerated functional recovery and increased GAP-43 expression at 7d. We detected early on in the recovery major transcriptional changes in both MABsallo and MABsallo-VEGF. MABSallo upregulated transcripts that encode proteins involved in myogenesis and dendrite development, and downregulated pro-inflammatory processes MABsallo-VEGF upregulated transcripts that encode proteins involved neuron and dendrite development and downregulates genes involved in hypoxia and oxidative stress. 7d after injury, Later MABsallo-VEGF showed a decrease in oxidative and inflammatory response compared to MABSallo treated urethras. These pathways are also downregulated in animals that have recovered at 7d, compared to non-recovered animals. Conclusion: Intra-arterial injection of MABsallo-VEGF enhances neuroregeneration and accelerates functional urethral and vaginal recovery after simulated vaginal delivery. Injection of stem cells induces faster recovery of urethral and vaginal function; cells overexpressing a factor increasing blood vessel formation, were even more effective.
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Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.
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Project description:The Wnt target gene Lgr5 marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A 3D culture system allows long-term clonal expansion of single Lgr5+ stem cells into transplantable organoids that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist Rspo, the recently discovered ligand of Lgr5. Here we show that Lgr5-LacZ is not expressed in healthy adult liver, yet that small Lgr5-LacZ+ cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signaling. As shown by lineage tracing using a novel Lgr5-ires-CreERT2 knock-in allele, damage-induced Lgr5+ cells generate hepatocytes and bile ducts in vivo. Single Lgr5+ cells from damaged liver can be clonally expanded as organoids in Rspo1-based culture medium over multiple months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into FAH-/- mice. These findings imply that previous findings on Lgr5+ stem cells in actively self-renewing tissues extend to damage-induced stem cells in a tissue with a low rate of spontaneous self-renewal. We first generated arrays from multiple wildtype tissues including muscle, white adipose tissues, brown adipose tissues, liver and pancreas. Then we generated arrays from liver derived cultures maintained in different conditions, and compared the expression profile with the corresponding parental tissues and other non-related tissues.
2013-01-28 | E-GEOD-32210 | biostudies-arrayexpress
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants. Suitable RNA was extracted from ten participants which were classified into two groups, the dryness and control groups, based on diagnosis of dryness by a nurse during gynecoligical examination.
2011-11-12 | E-GEOD-26761 | biostudies-arrayexpress