In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115477 | GEO | 2018/07/19
REPOSITORIES: GEO
Similar Datasets
Project description:Precursors for the male and female reproductive tracts (also known as the Wolffian duct and the Müllerian duct) co-exist in a mammalian embryo before sexual differentiation. The Wolffian duct and Müllerian duct are surrounded by their own mesenchymes in the mesonephros, which can be distinguished by their specific expression of Gli1 and Amhr2, respectively. In the XX embryo, during sexual differentiation, the Wolffian duct degenerates. In this study, by tracking the fate of the Gli1+ Wolffian duct mesenchyme in the tamoxifen inducible genetic lineage tracing model Gli1-CreER; Rosa-Tomato, we demonstrate that the Wolffian duct mesenchyme does not regress along with the Wolffian duct epithelium in the XX embryo. Instead, the Wolffian duct mesenchyme is repurposed and becomes a unique mesenchymal population in the female reproductive tract. Profiling the transcriptomes and chromatin accessibilities of the Gli1+ Wolffian duct mesenchyme in XX and XY during sexual differentiation (E14.5 and E16.5) shows signaling pathways and transcriptional factors that potentially involves the female and male fate differentiation of the Gli1+ Wolffian duct mesenchyme. Comparing the transcriptomes between the Gli1+ Wolffian duct mesenchyme and the Amhr2+ Müllerian duct mesenchyme from the neonatal uterus reveals similarities and differences between the two mesenchymal populations in the female reproductive tract. Ex vivo ablation of the Wolffian duct mesenchyme stunted the growth of the fetal female reproductive tract. In summary, our discovery of the contribution of the Wolffian duct mesenchyme to the female reproductive tract provides new insights into our understanding of sexual differentiation of reproductive tracts.
2022-10-05 | GSE179876 | GEO
Project description:Wolffian/epididymal duct morphogenesis highly coordinates with its specialized function of providing microenvironment for sperm maturation. Without normal development of Wolffian duct, male infertility will result. Therefore, it is important to understand the cellular and molecular mechanisms that regulated Wolffian duct morphogenesis. Our previous study showed that mediolateral intercalation of epithelial cells was a major driver of ductal elongation. In addition, radial intercalation of mesenchymal cells surrounding the duct also played roles in Wolffian duct morphogenesis, and all of these cell re-arrangements were regulated by protein tyrosine kinase 7 (PTK7), a member of the planar cell polarity (PCP) non-canonical Wnt pathway. In this study, we showed that PTK7 regulated assemblies of extracellular matrix (ECM) at the basement membrane and throughout the mesenchyme. Abnormal assembly of laminin, collagen IV, and nephronectin at the basement membrane and fibrosis-like deposition of fibrilla collagen in the interstitium were observed in Ptk7 knockout Wolffian ducts. Meanwhile, PTK7 regulated activity levels of small GTPase RAC1 and myosin II in the mesenchyme of the Wolffian duct. Activity levels of RAC1 and myosin II decreased in the Ptk7 knockout mesenchyme compared to controls. When in-vitro-cultured Wolffian ducts were treated with collagenase IV, cross-link of fibrilla collagen was reduced, Wolffian duct elongation and coiling was reduced significantly, and cyst-like bulge was developed in the epithelial duct. When Wolffian ducts were treated with RAC1 inhibitor NSC23766, fibrilla collagen in the mesenchyme was disassembled, and Wolffian duct elongation was suppressed significantly. Our finding suggested that PTK7 regulated ECM assembly in the mesenchyme likely through regulating RAC1 and myosin II activities. Dynamic assembly and remodeling of ECM were important to Wolffian duct morphogenesis.
2018-05-09 | GSE98715 | GEO
Project description:Wolffian duct maintenance and differentiation is predominantly driven by the androgen action, which is mediated by the androgen receptor (AR). It is well established that the mesenchyme indicates the fate and differentiation of epithelial cells. However, in vivo developmental requirement of mesenchymal AR in Wolffian duct development is still undefined. By designing a mesenchyme-specific Ar knockout (ARKO), we discovered that the loss of mesenchymal Ar led to the bilateral or unilateral degeneration of caudal Wolffian ducts and cystic formation at the cranial Wolffian ducts. Ex vivo culture of ARKO Wolffian ducts invariably resulted in bilateral defects, suggesting that some factor(s) originating from surrounding tissues in vivo might promote Wolffian duct survival and growth even in the absence of mesenchymal Ar. Mechanistically, we found cell proliferation was significantly reduced in both epithelial and mesenchymal compartments; but cell apoptosis was not affected. Transcriptomic analysis by RNA-seq revealed differentially expressed genes associated with morphological and cellular changes in ARKO male embryos (i.e. reduced cell proliferation and decreased number of epithelial cells). Mesenchymal differentiation into smooth muscle cells that are critical for morphogenesis was also impaired in ARKO male embryos. Taken together, our results demonstrate the crucial roles of the mesenchymal AR in Wolffian duct maintenance and morphogenesis in mice.
2024-01-10 | GSE246141 | GEO
Project description:In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells
| PRJNA475133 | ENA
Project description:Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
2009-05-20 | GSE15770 | GEO
Project description:Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
2009-05-20 | GSE15768 | GEO
Project description:Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
2009-05-20 | GSE15772 | GEO
Project description:In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we preformed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of COUP-TFII’s potential transcriptional partners in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.
2022-04-20 | GSE157836 | GEO
Project description:The airway epithelium is in contact with the environment and therefore constantly at risk for injury. Basal cells have been found to repair the surface epithelium, but the contribution of other stem cell populations to airway epithelial repair have not been identified. We demonstrated that airway submucosal gland duct cells, in addition to basal cells, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and basal cells. We found that only duct cells were capable of regenerating submucosal gland tubules and ducts, as well as the surface epithelium overlying the submucosal glands. This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases. Murine proximal airway duct and basal cells were isolated from 8-12 week old male and female mice and FACS sorted. Each sample contains cells that were sorted from a different pool of 10-15 C57Bl/6 mice. RNA was extracted, labeled, and hybridized to Affymetrix Mouse Genome 430 2.0 Array (GPL1261)
2012-05-31 | E-GEOD-28651 | biostudies-arrayexpress
Project description:The airway epithelium is in contact with the environment and therefore constantly at risk for injury. Basal cells have been found to repair the surface epithelium, but the contribution of other stem cell populations to airway epithelial repair have not been identified. We demonstrated that airway submucosal gland duct cells, in addition to basal cells, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and basal cells. We found that only duct cells were capable of regenerating submucosal gland tubules and ducts, as well as the surface epithelium overlying the submucosal glands. This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases.
2012-06-01 | GSE28651 | GEO