Heparan sulfate determines myofibroblast identity during alveolar morphogenesis (scRNA-seq)
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ABSTRACT:
PROVIDER: PRJNA1102279 | ENA |
REPOSITORIES: ENA
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Project description:Heparan sulfate determines myofibroblast identity during alveolar morphogenesis
| PRJNA1102274 | ENA
Project description:Heparan sulfate determines myofibroblast identity during alveolar morphogenesis (ATAC-seq)
| PRJNA1102278 | ENA
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.
2025-02-04 | GSE264372 | GEO
Project description:Standardized skin wounds were established surgically on mice and allowed to heal during a 15-day period. Expression of genes related to heparan sulfate biosynthesis was studied in wound bed and edges during the healing process. Keywords: Time course
2008-04-01 | GSE7435 | GEO
Project description:Our specific aim is to examine differential expression of sulf-1 and sulf-2, enzymes involved in heparan sulfate biosynthesis, as well as Wnt ligands and Wnt signaling mediators during corneal wound healing using a mouse corneal scratch model. The specific structural features of heparan sulfate underlie its role in modulating cellular responses to growth factors such as the Wnts. Heparan sulfate 6-O-endosulfatases (sulf-1 and sulf-2) remove 6-O sulfate group from trisulfated disaccharides present on heparan sulfate chains. Our preliminary results suggest that sulf-1 is upregulated at the protein level in the epithelial cells of wounded mouse corneas, as compared to the undamaged contralateral eye. Modulation of heparan sulfate proteoglycan expression and/or structural modifications of its chains might be an important aspect of the regulation of epithelial cell migration and proliferation during wound healing.
2011-04-29 | GSE28931 | GEO
Project description:The arterial endothelium’s response to its flow environment is critical to vascular homeostasis. The endothelial glycocalyx has been shown to play a major role in mechanotransduction, but the extent to which the components of the glycocalyx affect the overall function of the endothelium remains unclear. The objective of this study was to further elucidate the role of heparan sulfate as a mechanosensor on the surface of the arterial endothelium, by (1) expanding the variety of shear waveforms investigated, (2) continuously suppressing heparan sulfate expression rather than using a pre-flow batch treatment, and (3) performing microarray analysis on post-flow samples. Porcine aortic endothelial cells were exposed to non-reversing, reversing, and oscillatory shear waveforms for 24 hours with or without continuous heparan sulfate suppression with heparinase. All shear waveforms significantly increased the amount of heparan sulfate on the surface of the endothelium. Suppression of heparan sulfate to less than 25% of control levels did not inhibit shear-induced cell alignment or nitric oxide production, or alter gene expression, for any of the shear waveforms investigated. We infer that heparan sulfate on the surface of porcine aortic endothelial cells is not the primary mechanosensor for many shear-responsive endothelial cell functions in this species.
2011-07-22 | GSE30843 | GEO
Project description:Standardized skin wounds were established surgically on mice and allowed to heal during a 15-day period. Expression of genes related to heparan sulfate biosynthesis was studied in wound bed and edges during the healing process. Total RNA was isolated from wound edge (regenerating skin) and wound bed at 2, 6 and 15 days post wounding, as well as from intact control skin. Three animals were used for each time point.
2010-05-22 | E-GEOD-7435 | biostudies-arrayexpress
Project description:The arterial endothelium’s response to its flow environment is critical to vascular homeostasis. The endothelial glycocalyx has been shown to play a major role in mechanotransduction, but the extent to which the components of the glycocalyx affect the overall function of the endothelium remains unclear. The objective of this study was to further elucidate the role of heparan sulfate as a mechanosensor on the surface of the arterial endothelium, by (1) expanding the variety of shear waveforms investigated, (2) continuously suppressing heparan sulfate expression rather than using a pre-flow batch treatment, and (3) performing microarray analysis on post-flow samples. Porcine aortic endothelial cells were exposed to non-reversing, reversing, and oscillatory shear waveforms for 24 hours with or without continuous heparan sulfate suppression with heparinase. All shear waveforms significantly increased the amount of heparan sulfate on the surface of the endothelium. Suppression of heparan sulfate to less than 25% of control levels did not inhibit shear-induced cell alignment or nitric oxide production, or alter gene expression, for any of the shear waveforms investigated. We infer that heparan sulfate on the surface of porcine aortic endothelial cells is not the primary mechanosensor for many shear-responsive endothelial cell functions in this species. Porcine aortic endothelial cells were exposed to 3 different shear waveforms for 24 hours with or without the addition of 300 mU/ml heparinase III to the flow media. The shear waveforms inculded Non-reversing (15 ± 15 dyne/cm2, 1 Hz), Steady (15 dyne/cm2), or Oscillatory (0 ± 15 dyne/cm2, 1 Hz) shear. Four replicates of each condition were performed for a total of 24 experiments. Each experimental sample was hybridized to an oligonucleotide array along with a standard reference sample (static cells).
2011-07-21 | E-GEOD-30843 | biostudies-arrayexpress