Expression data from 5-week-old mouse prostate
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Xuanyang Li
PROVIDER: E-GEOD-46898 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Heparan sulfate (HS) is a linear, sulfated polysaccharide, and expresses abundantly in prostate and PCa tissues. Intriguingly, the HS content and sulfation modifications appear to increase when the prostate becomes malignance, suggesting that HS may critically modulate PCa pathogenesis. We specifically ablated Ext1, the enzyme that initiates HS biosynthesis, in mouse prostate at late development stage. And used microarray to detail the gene expressions affected by Ext1 ablation and identified distinct classes of up-regulated genes during this process.
2013-05-15 | GSE46898 | GEO
Project description:Heparan (HS) proteoglycans (HSPGs) are common on the cell surface and mediate many physiological processes. Binding of HSPG ligands is determined by the sulfation code on the heparan sulfate chain and the HS chain can be N-/2-O/6-O- or 3-O-sulfated, generating a heterogenous sulfation pattern. 3-O sulfated HS (3S-HS) have been reported to play a role in several pathological processes such as the coagulation system, viral pathogenesis, or in the binding and internalization of tau in Alzheimer’s disease. Few 3S-HS-specific interactors are known and the role of 3S-HS in health and disease is limited, especially in the central nervous system. Using human CSF as a surrogate for the extracellular compartment of the CNS, we determined the interactome of synthetic heparan sulfate oligosaccharides with defined sulfation patterns. These AE-MS studies significantly expand the proteins that can interact with HS and for which 3O sulfation is required. LRP1 was found as a novel 3S-HS interactor, requiring GlcA-GlcNS6S3S for binding, similar to ATIII. Both interactions were validated via Western blot. Our dataset brings forward new HS and 3S-HS ligands which can be pertinent to unravel molecular mechanisms dependent on 3S-HS in (patho)physiological conditions.
2022-08-09 | PXD034935 | Pride
Project description:Embryonic stem (ES) cells continuously decide whether to maintain pluripotency or differentiate. While exogenous LIF and BMP4 perpetuate a pluripotent state, less is known about factors initiating differentiation. We show that heparan sulfate (HS) proteoglycans are critical co-receptors for signals inducing ES cell differentiation. Genetic targeting of NDST1 and 2, two enzymes required for N-sulfation of proteoglycans, blocked differentiation. This phenotype was rescued by HS presented in trans or by soluble heparin. NaClO3-, which reduces sulfation of proteoglycans, potently blocked differentiation of wild type cells. Mechanistically, N-sulfation was identified to be critical for functional autocrine FGF4 signalling. Micro array analysis identified the pluripotency maintaining transcription factors Nanog, KLF2/4/8, Tbx3 and Tcf3 to be negatively regulated, whereas markers of differentiation such as Gbx2, Dnmt3b, FGF5 and Brachyury were induced by sulfation-dependent-FGFR signalling. We show that several of these genes are heterogeneously expressed in ES cells and targeting of heparan sulfation or FGFR-signalling facilitated a homogenous Nanog/KLF4/Tbx3 positive ES cell state. This finding suggests that the recently discovered heterogeneous state of ES cells is regulated by HS-dependent FGFR signalling. Similarly, culturing blastocysts with NaClO3- eliminated GATA6 positive primitive endoderm progenitors generating a homogenous Nanog positive inner cell mass. Functionally, reduction of sulfation robustly improved de novo ES cell derivation efficiency. We conclude that N-sulfated HS is required for FGF4 signalling to maintain ES cells primed for differentiation in a heterogeneous state. Inhibiting this pathway facilitates a more naïve ground state. Four groups with three biological replicates and a technical duplicate in each
2010-04-09 | E-GEOD-15974 | biostudies-arrayexpress
Project description:Embryonic stem (ES) cells continuously decide whether to maintain pluripotency or differentiate. While exogenous LIF and BMP4 perpetuate a pluripotent state, less is known about factors initiating differentiation. We show that heparan sulfate (HS) proteoglycans are critical co-receptors for signals inducing ES cell differentiation. Genetic targeting of NDST1 and 2, two enzymes required for N-sulfation of proteoglycans, blocked differentiation. This phenotype was rescued by HS presented in trans or by soluble heparin. NaClO3-, which reduces sulfation of proteoglycans, potently blocked differentiation of wild type cells. Mechanistically, N-sulfation was identified to be critical for functional autocrine FGF4 signalling. Micro array analysis identified the pluripotency maintaining transcription factors Nanog, KLF2/4/8, Tbx3 and Tcf3 to be negatively regulated, whereas markers of differentiation such as Gbx2, Dnmt3b, FGF5 and Brachyury were induced by sulfation-dependent-FGFR signalling. We show that several of these genes are heterogeneously expressed in ES cells and targeting of heparan sulfation or FGFR-signalling facilitated a homogenous Nanog/KLF4/Tbx3 positive ES cell state. This finding suggests that the recently discovered heterogeneous state of ES cells is regulated by HS-dependent FGFR signalling. Similarly, culturing blastocysts with NaClO3- eliminated GATA6 positive primitive endoderm progenitors generating a homogenous Nanog positive inner cell mass. Functionally, reduction of sulfation robustly improved de novo ES cell derivation efficiency. We conclude that N-sulfated HS is required for FGF4 signalling to maintain ES cells primed for differentiation in a heterogeneous state. Inhibiting this pathway facilitates a more naïve ground state.
2009-11-13 | GSE15974 | GEO
Project description:Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan protein cores are modified by sulfotransferases in a highly ordered series of biosynthetic steps resulting in immense structural diversity due to negatively charged sulfate modifications. 3-O-sulfation is the least abundant modification generated by a family of seven isoforms but creates the most highly sulfated HS domains. We analyzed the kidney phenotypes in the Hs3st3a1, Hs3st3b1 and Hs3st6 -knockout (KO) mice, the isoforms enriched in kidney podocytes. Individual KO mice show no overt kidney phenotype, although Hs3st3b1 kidneys were smaller than wildtype (WT). Furthermore, Hs3st3a1-/-; Hs3st3b1-/- double knockout (DKO) kidneys were smaller but also had a reduction in glomerular size relative to wildtype (WT). Mass spectrometry analysis of kidney HS showed reduced 3-O-sulfation in Hs3st3a1-/- and Hs3st3b1-/-, but not in Hs3st6-/- kidneys. Glomerular HS showed reduced HS staining and reduced ligand-and-carbohydrate engagement (LACE) assay, a tool that detects changes in binding of growth factor receptor-ligand complexes to HS. Interestingly, DKO mice have increased levels of blood urea nitrogen, although no differences were detected in urinary levels of albumin, creatinine and nephrin. Finally, transmission electron microscopy showed irregular and thickened GBM and podocyte foot process effacement in the DKO compared to WT. Together, our data suggest that loss of 3-O-HS domains disrupts the kidney glomerular architecture without affecting the glomerular filtration barrier and overall kidney function.
2024-07-05 | GSE261059 | GEO
Project description:FGF signaling is essential for salivary gland (SG) development and heparan sulfate (HS) regulation of FGFR function is determined by immense structural diversity of sulfated HS domains. The basement membrane (BM), containing HS proteoglycans, collagens and laminins, separates epithelia from stroma and controls growth factor-matrix cross-talk. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS) and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs), which produce BM and are a growth factor signaling hub. To investigate 3-O-HS regulation of MEC function and growth factor signaling, we generated Hs3st3a1;Hs3st3b1 double knockout (DKO) mice. The DKO HS loses specific highly 3-O-sulfated tetrasaccharides, which increases FGF/FGFR-complex binding to HS. During development this leads to increased FGFR-, BM- and MEC-related gene expression. However, in adult DKO SGs the secretory units containing acinar and MECs, have reduced MECs, increased BM and disrupted acinar polarity, resulting in salivary hypofunction. We used defined 3-O-sulfated-HS in FGFR pulldown assays and primary organ cultures to investigate 3-O-HS-dependent mechanisms regulating MEC development. We find that 3-O-HS modulates FGFR signaling to regulate MEC BM synthesis which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.
2024-08-02 | GSE235184 | GEO
Project description:FGF signaling is essential for salivary gland (SG) development and heparan sulfate (HS) regulation of FGFR function is determined by immense structural diversity of sulfated HS domains. The basement membrane (BM), containing HS proteoglycans, collagens and laminins, separates epithelia from stroma and controls growth factor-matrix cross-talk. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS) and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs), which produce BM and are a growth factor signaling hub. To investigate 3-O-HS regulation of MEC function and growth factor signaling, we generated Hs3st3a1;Hs3st3b1 double knockout (DKO) mice. The DKO HS loses specific highly 3-O-sulfated tetrasaccharides, which increases FGF/FGFR-complex binding to HS. During development this leads to increased FGFR-, BM- and MEC-related gene expression. However, in adult DKO SGs the secretory units containing acinar and MECs, have reduced MECs, increased BM and disrupted acinar polarity, resulting in salivary hypofunction. We used defined 3-O-sulfated-HS in FGFR pulldown assays and primary organ cultures to investigate 3-O-HS-dependent mechanisms regulating MEC development. We find that 3-O-HS modulates FGFR signaling to regulate MEC BM synthesis which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.
2024-08-02 | GSE235185 | GEO
Project description:Heparan sulfate proteoglycans (HSPGs) are expressed on virtually all animal cells and are involved in many important biological processes. Each HSPG consists of a core protein with one or more covalently attached linear heparan sulfate (HS) chains composed of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues of HS specify the location of distinct ligand binding sites on the cell surface, and these modifications can vary temporally during development and spatially across tissues. While most of the enzymes involved in HS biosynthesis have been studied extensively, much less information exists regarding the specific mechanisms that give rise to the variable composition and binding properties of HS.
2021-01-28 | GSE145789 | GEO
Project description:Heparan sulfate proteoglycans (HSPGs) are expressed on virtually all animal cells and are involved in many important biological processes. Each HSPG consists of a core protein with one or more covalently attached linear heparan sulfate (HS) chains composed of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues of HS specify the location of distinct ligand binding sites on the cell surface, and these modifications can vary temporally during development and spatially across tissues. While most of the enzymes involved in HS biosynthesis have been studied extensively, much less information exists regarding the specific mechanisms that give rise to the variable composition and binding properties of HS.
2021-01-28 | GSE163162 | GEO
Project description:Heparan sulfate (HS) is a linear polysaccharide that plays a key role in cellular signaling networks. HS functions are regulated by its 6-O-sulfation, which is catalyzed by HS 6-O-sulfotransferases (HS6STs). Although mutations in HS6ST2 cause intellectual disability in human patients, the role and molecular mechanisms of HS6ST2 in the adult mammalian brain remain unknown. Here we found that the brain specifically expresses the long isoform of Hs6st2, which encodes a protein that retains the sulfotransferase domain and acquires a novel sub-structure. To determine the role of Hs6st2 in the brain, we carried out a series of behavioral and molecular assessments on the Hs6st2 knockout mice. We found that Hs6st2 knockout mice exhibit high body weight, hyperactivity, and memory-related deficits. To determine the molecular mechanisms underlying these deficits, we carried out strong anion exchange-high performance liquid chromatography and RNA sequencing. We found that knockout of Hs6st2 decreases HS 6-O-sulfation levels in the brain and impairs transcriptome in the hippocampus. We also found that the transcriptome changes are enriched in genes involved in ribosome and protein translation pathways, which are likely due to the downregulation of the fibroblast growth factor signaling. Together, our study demonstrates the role and molecular mechanisms of Hs6st2 in the adult mammalian brain, which provides new insights into the role of HS in brain health and disease.
2024-08-04 | GSE213745 | GEO