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To examine the expression of Sulf1 and Sulf2, as well as other glycan-related genes, in human Idiopathic pulmonary fibrosis (IPF) lungs compared to normal lung samples

ABSTRACT: Microarray analysis to examine glycan-related gene expression in idiopathic pulmonary fibrosis Heparan sulfate 6-O-endosulfatases (Sulf1 and Sulf2) remove 6-O sulfate groups from heparan sulfate intra-chain sites on the cell surface and in the extracellular matrix, and modulate the functions of many growth factors and morphogens including FGF, Wnt and TGF-beta. Works from our laboratory have shown that TGF-beta 1 induces Sulf1 and Sulf2 expression in a cell-type specific manner in the lung, specifically Sulf1 in lung fibroblasts and Sulf2 in type II alveolar epithelial cells. Interestingly TGF-beta 1-induced Sulf1 and Sulf2 in turn modulate TGF-beta 1 function in culture.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31934 | GEO | 2011/09/06

SECONDARY ACCESSION(S): PRJNA145033

REPOSITORIES: GEO

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To examine the expression of Sulf1 and Sulf2, as well as other glycan-related genes, in human Idiopathic pulmonary fibrosis (IPF) lungs compared to normal lung samples

Project description:Microarray analysis to examine glycan-related gene expression in idiopathic pulmonary fibrosis Heparan sulfate 6-O-endosulfatases (Sulf1 and Sulf2) remove 6-O sulfate groups from heparan sulfate intra-chain sites on the cell surface and in the extracellular matrix, and modulate the functions of many growth factors and morphogens including FGF, Wnt and TGF-beta. Works from our laboratory have shown that TGF-beta 1 induces Sulf1 and Sulf2 expression in a cell-type specific manner in the lung, specifically Sulf1 in lung fibroblasts and Sulf2 in type II alveolar epithelial cells. Interestingly TGF-beta 1-induced Sulf1 and Sulf2 in turn modulate TGF-beta 1 function in culture. The aim of this study is to examine the expression of Sulf1 and Sulf2 as well as other glycan-related genes (heparan biosynthetic enzymes, TGF-beta, FGF and Wnt signaling pathway components) in human idiopathic pulmonary fibrosis (IPF) lungs compared to normal lung samples. We will examine gene expression in triplicate samples from RNA of total lung homogenates from IPF and control (normal) lungs

2011-09-05 | E-GEOD-31934 | biostudies-arrayexpress

Transcriptional control of Sulf1 by WT1 primes epicardial signalling and fate by modifying extracellular heparan sulfate status [ATAC-Seq]

Project description:Considering the transcriptional correlations we observed between WT1 and 6-O-endosulfatases in the epicardium, we sought to elucidate whether WT1 regulates 6-O-endosulfatase expression directly and how its binding may differ between Sulf1 and Sulf2 in the epicardium. We first assessed the landscape of chromatin accessibility in FACS sorted epicardial cells at E13.5 (CD31-tdTomato+PDPN+), and employed TOBIAS footprinting to identify candidate WT1 binding sites in the Sulf1 and Sulf2 loci. This analysis predicted WT1 binding to the highly accessible Sulf1 promoter but no binding was predicted for Sulf2. As expected, there was lower accessibility in this locus which reflected reduced Sulf2 gene activity in the epicardial layer.

2026-08-06 | GSE299995 | GEO

Transcriptional control of Sulf1 by WT1 primes epicardial signalling and fate by modifying extracellular heparan sulfate status [CUT&Run]

Project description:Considering the transcriptional correlations we observed between WT1 and 6-O-endosulfatases in the epicardium, we sought to elucidate whether WT1 regulates 6-O-endosulfatase expression directly and how its binding may differ between Sulf1 and Sulf2 in the epicardium. We employed CUT&RUN-seq experiments that mapped genome-wide binding sites of WT1 and histone modifications in cultured epicardial cells (MEC1). We identified weak, although variable, binding of WT1 to the Sulf1 promoter and significant WT1 binding to an intronic enhancer, marked by active chromatin modification H3K27ac, located in intron 1 of the Sulf1 gene. Interestingly, the CUT&RUN-seq experiments also revealed significant binding of WT1 to the third intron of the Sulf2 gene, displaying chromatin accessibility without any histone marks or gene activity.

2026-08-06 | GSE299998 | GEO

Transcriptional control of Sulf1 by WT1 primes epicardial signalling and fate by modifying extracellular heparan sulfate status [scRNA-Seq]

Project description:Despite their decisive influence over the signalling that underlies cardiac morphogenesis, the expression of core HSPGs and the enzymes that give rise to distinct spatiotemporal sulfation patterning have not been well documented in the developing heart. In the present study, we systematically profiled 6-O-endosulfatases and target HSPGs expression in the embryonic mouse heart. We found that HSPGs are dynamically expressed, with cell-type specific expression, and changing tissue composition contributing to HSPG diversity in the developing embryonic heart. We identified cell type-specific expression patterns for Sulf1 and Sulf2, that changed over the course of development, unrelated to lineage or embryonic origin. We reveal Sulf1 as the major 6-O-endosulfatase expressed in the epicardium.

2026-08-06 | GSE299996 | GEO

Heparan sulfate Sulfatases are essential for the patterning of human stem cell-derived midbrain dopaminergic neurons

Project description:Midbrain dopaminergic neurons (mDA) are selectively lost in Parkinson’s disease (PD), driving sustained efforts to generate bona fide mDA neurons from human-induced pluripotent stem cells (iPSCs) for replacement therapy. While morphogen gradients and transcription factors have been extensively studied, extracellular regulators remain largely overlooked. Here, we identify the heparan sulfate-modifying enzymes SULF1 and SULF2 as essential for establishing mDA neuron identity in vitro. Using CRISPR/Cas9-engineered iPSCs, we show that loss of SULF1/2 increases 6-O-sulfation of heparan sulfate chains and disrupts anterior-posterior and dorsoventral patterning in cells exposed to a midbrain differentiation protocol. Double-knockout cells fail to acquire midbrain fate and instead adopt caudal and neural crest-like identities, as revealed by single-nucleus RNA sequencing. Mechanistically, we find enhanced FGF signaling and demonstrate that FGF inhibition redirects cells toward midbrain progenitors, without fully restoring ventral identity. These findings establish a critical role for SULF1/2 in human mDA neuron development and uncover a previously unrecognized layer of extracellular control over neuronal patterning, opening for novel strategies to refine differentiation protocols for PD and beyond.

2026-07-16 | PXD075443 | Pride

Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.

Project description:Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and SULF2, which encodes an extracellular heparan sulfate 6-O-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression, and similar to silencing of TP53, RNA interference-mediated suppression of SULF2 results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology. Expression profiling experiments were performed to perturb the p53 status in cancer cell lines as a means of identifying novel members of the p53 pathway.

2010-06-20 | E-GEOD-15440 | biostudies-arrayexpress

Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.

2009-04-01 | GSE15440 | GEO

Heparan sulfate modifications of betaglycan promote TIMP3-dependent ectodomain shedding to fine-tune TGF-β signaling.

Project description:Betaglycan/type III TGF-β receptor (TGFBR3) is an established co-receptor for the TGF-β superfamily with direct binding demonstrated for TGF-β 1-3 and inhibin A. Betaglycan can be membrane-bound or have its ectodomain cleaved/ shed to produce soluble-betaglycan that has been demonstrated to sequester ligands. Extracellular domain of betaglycan is modified with glycosaminoglycan chains at Ser residues S534 and S545, to which heparan sulfate and chondroitin sulfate chains are covalently attached. To delineate the contribution of the heparan and chondroitin sulfate modifications on betaglycan on its shedding and thereby on TGF-β signaling in ovarian cancer biology, we used mutants of betaglycan with alterations to the different glycosaminoglycan modifications. We made the unexpected discovery that the heparan sulfate modifications are essential for maximum ectodomain shedding of betaglycan, which is further essential for the ability of betaglycan to suppress TGF-β signaling and the tumor cells responses to exogenous TGF-β ligand. Using unbiased transcriptomics, we identified TIMP3 as a key regulator of betaglycan shedding and thereby TGF-β signaling. Taken together, these studies are the first to demonstrate a critical link between the well-known modifications on betaglycan and TGF-β signaling responses.

2024-02-21 | GSE237403 | GEO

Heparan sulfate Sulfatases are essential for the patterning of stem cell–derived midbrain dopaminergic neurons

Project description:Midbrain dopaminergic (mDA) neuron loss underlies Parkinson’s disease (PD), making it critical to understand how mDA identity is established during development for cell replacement therapy. While intrinsic transcriptional programs and morphogen gradients driving mDA are known, the contribution of extracellular modulators remains less explored. Here, we show that the heparan sulfate (HS)–modifying enzymes SULF1 and SULF2 are essential for proper mDA neuron differentiation in vitro. Using CRISPR/Cas9-engineered human iPSCs, we demonstrate that SULF1/2 double knockout (DKO) cells fail to acquire ventral midbrain identity and instead adopt dorso-caudal fates, marked by ectopic expression of CDX2, HOX genes, neural crest, and Schwann cell markers. Mechanistically, SULF1/2 loss leads to increased 6-O-sulfation of HS chains, enhancing FGF signaling. FGF inhibition in SULF1/2 DKO cells suppresses CDX2+ axial progenitors and caudal derivatives, but does not completely restore ventral midbrain identity. Instead, it redirects cells toward dorsal lineages, including the emergence of ependymal-like cells. Our findings identify SULF1/2 as key modulators of anterior-posterior and dorsal-ventral patterning during mDA neuron development, possibly acting through a tight control of signaling molecules balance, and offer insights to refine differentiation protocols for PD cell therapy.

2026-07-13 | GSE300452 | GEO

Examine differential expression of sulf-1 and sulf-2, enzymes involved in heparan sulfate biosynthesis

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