Similar Datasets
Project description:Postnatal respiration requires the bulk formation of alveoli that produces extensive surface area for gas diffusion from epithelium to the circulatory system. Alveolar morphogenesis initiates at late gestation or postnatal stage during mammalian development and is mediated by coordination among epithelial, mesenchymal and endothelial cells. Here we show that stromal cells produce Heparan Sulfate Glycosaminoglycan (HS-GAG) to maintain a niche for alveolar development by modulating both the biophysical and biochemical cues. HS is predominantly enriched in myofibroblasts in postnatal murine lungs, and genetic ablation of HS synthase gene Ext1 in fibroblast populations results in enlarged and simplified alveolar structures. HS is selectively required for the cell identity of a subset of alveolar myofibroblasts (PDGFRαhi αSMA+) residing in the distal alveolar region, which exhibit contractile properties and maintain WNT signaling activity to support normal proliferation and differentiation of alveolar epithelial cells. HS is essential to prevent precocious apoptosis of alveolar myofibroblasts. We show that these processes are dependent upon FGF/MAPK signaling and forced activation of MAPK/ERK signaling partially corrected alveolar simplification along with restoration of alveolar myofibroblast identity and AT2 cell proliferation in HS deficient mice. These data reveal HS as an essential orchestrator for developing alveolar niche critical for generation of gas exchange units.
2025-02-05 | GSE264371 | GEO
Project description:Postnatal respiration requires the bulk formation of alveoli that produces extensive surface area for gas diffusion from epithelium to the circulatory system. Alveolar morphogenesis initiates at late gestation or postnatal stage during mammalian development and is mediated by coordination among epithelial, mesenchymal and endothelial cells. Here we show that stromal cells produce Heparan Sulfate Glycosaminoglycan (HS-GAG) to maintain a niche for alveolar development by modulating both the biophysical and biochemical cues. HS is predominantly enriched in myofibroblasts in postnatal murine lungs, and genetic ablation of HS synthase gene Ext1 in fibroblast populations results in enlarged and simplified alveolar structures. HS is selectively required for the cell identity of a subset of alveolar myofibroblasts (PDGFRαhi αSMA+) residing in the distal alveolar region, which exhibit contractile properties and maintain WNT signaling activity to support normal proliferation and differentiation of alveolar epithelial cells. HS is essential to prevent precocious apoptosis of alveolar myofibroblasts. We show that these processes are dependent upon FGF/MAPK signaling and forced activation of MAPK/ERK signaling partially corrected alveolar simplification along with restoration of alveolar myofibroblast identity and AT2 cell proliferation in HS deficient mice. These data reveal HS as an essential orchestrator for developing alveolar niche critical for generation of gas exchange units.
2025-02-05 | GSE264370 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-09-28 | E-GEOD-60249 | biostudies-arrayexpress
Project description:Heparan sulfate proteoglycans (HSPGs) have been shown to regulate various developmental processes. However, the function of heparan sulfate (HS) during the development of mammalian stomach has not been characterized yet. Here, we investigate the role of epithelial HS in embryonic stomach by examining mice deficient in the glycosyltransferase gene Ext1 We show that HS exhibits a specific and dynamic expression pattern in mouse embryonic stomach. Depletion of the epithelial HS leads to stomach hypoplasia, with phenotypic differences in the gastric mucosa between the forestomach and hindstomach. In the posterior stomach, HS depletion disrupts glandular stomach patterning and cytodifferentiation via attenuation of Fgf signaling activity. Inhibition of Fgf signaling in vitro recapitulates the patterning defect. Ligand and carbohydrate engagement assay (LACE) reveals a diminished assembly of Fgf10 and Fgfr2b in the mutant. In the anterior stomach, loss of epithelial HS leads to stratification and differentiation defects of the multilayered squamous epithelium, along with reduced Hh and Bmp signaling activity. Our data demonstrate that epithelial HS plays multiple roles in regulating mammalian stomach morphogenesis in a regional-specific manner.
| S-EPMC6031332 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-20 | GSE83505 | GEO
Project description:Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous epithelial-mesenchymal interactions. Once the first HF cycle is complete it repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans are found on the cell surface and in the extracellular matrix where they influence a variety of biological processes by interacting with physiologically important proteins, such as growth factors. Inhibition of heparanase (an HS endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like process. Therefore, this study aimed to elucidate the precise role of HS in HF morphogenesis and cycling. An inducible tetratransgenic mouse model was generated to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from P21. Interestingly, EXT1(StEpiΔ/StEpiΔ) mice presented solely anagen HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair regrowth in the EXT1(StEpiΔ/StEpiΔ) mice and hindered cycling into catagen. The ablation of HS in the interfollicular epidermal cells of mature skin led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic Hedgehog signaling pathway regulates HF formation during embryogenesis and prevents HF formation in mature skin. Finally, the knock-out of HS also led to the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature mice, leading to exacerbated sebum production and accumulation on the skin surface. Therefore, our findings clearly show that an intricate control of HS levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF cycling.
| S-EPMC4155684 | biostudies-literature
Project description:The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation of the common proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS was shown to be virtually abolished, whereas these mutants still were capable of synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further, extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1 double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular matrix surrounding chondrocytes.
| S-EPMC3460485 | biostudies-literature
Project description:The developmental activities of morphogens depend on the gradients that they form in the extracellular matrix. Here, we show that differences in the binding of fibroblast growth factor 7 (FGF7) and FGF10 to heparan sulfate (HS) underlie the formation of different gradients that dictate distinct activities during branching morphogenesis. Reducing the binding affinity of FGF10 for HS by mutating a single residue in its HS-binding pocket converted FGF10 into a functional mimic of FGF7 with respect to gradient formation and regulation of branching morphogenesis. In particular, the mutant form of FGF10 caused lacrimal and salivary gland epithelium buds to branch rather than to elongate. In contrast, mutations that reduced the affinity of the FGF10 for its receptor affected the extent, but not the nature, of the response. Our data may provide a general model for understanding how binding to HS regulates other morphogenetic gradients.
| S-EPMC2884999 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-09-28 | GSE60249 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-01 | GSE235187 | GEO