Biology subjects

van der Vlag, J.

Publications and source records attributed to van der Vlag, J..

3 recordsLinked to original sources

bioRxiv2024

Glycoinformatic profiling of label-free intact heparan sulfate oligosaccharides

Heparan sulfates (HS) are a group of heterogenous linear, sulfated polysaccharides that play a role in in health and many diseases including cancer, cardiovascular, and kidney diseases. The structural variety of HS has greatly challenged the development and utility of HS analytics, particularly for native structures, leaving a significant gap in HS technologies for clinical application. Mass spectrometry (MS)-based profiling with bioinformatics offers a top-down approach that can retain variety in large data sets. Using healthy human plasmas, we developed an MS glycoprofiling approach for native HS oligosaccharides, which retains the structural complexity of each individual HS chain and generates an HS index (or Heparan-ome) for each patient. As a proof of concept, analysis of 56 plasma samples ranging from 6 groups of kidney disease patients revealed a new subset cluster (20%, 4/20) of membranous glomerulopathy (MG) patients with distinct HS profiles, highlighting the potential of HS glycoprofiling as a powerful new approach into clinical practice, which warrants future development into clinical diagnostics of kidney and other diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/613784v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@6dac34org.highwire.dtl.DTLVardef@449da1org.highwire.dtl.DTLVardef@c8eb88org.highwire.dtl.DTLVardef@df4deb_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling

Nephrotic syndrome (NS) is characterized by severe proteinuria as a consequence of kidney glomerular injury due to podocyte damage. In vitro models mimicking in vivo podocyte characteristics are a prerequisite to resolve NS pathogenesis. Here, we report human induced pluripotent stem cell derived kidney organoids containing a podocyte population that heads towards adult podocytes and were superior compared to 2D counterparts, based on scRNA sequencing, super-resolution imaging and electron microscopy. In this study, these next-generation podocytes in kidney organoids enabled personalized idiopathic nephrotic syndrome modeling as shown by activated slit diaphragm signaling and podocyte injury following protamine sulfate treatment and exposure to NS plasma containing pathogenic permeability factors. Organoids cultured from cells of a patient with heterozygous NPHS2 mutations showed poor NPHS2 expression and aberrant NPHS1 localization, which was reversible after genetic correction. Repaired organoids displayed increased VEGFA pathway activity and transcription factor activity known to be essential for podocyte physiology, as shown by RNA sequencing. This study shows that organoids are the preferred model of choice to study idiopathic and congenital podocytopathies. Summary StatementKidney organoid podocytes allow personalized nephrotic sydrome modeling,

molecular biology↗

bioRxiv2020

Role of syndecan-1 in the interaction between dendritic cells and T cells

Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that can bind cytokines and chemokines via its heparan sulfate side chains, and has immunomodulatory properties in experimental models. Sdc-1 expression has been reported on dendritic cells (DC) and T cells. The potential role of Sdc-1 in DC - T cell interaction has not been investigated yet. We postulate that Sdc-1 is involved in DC - T cell interaction and may influence graft survival in an allogeneic transplant model. Sdc-1 expression on bone marrow-derived DC and T cells was analyzed by flow cytometry. Unstimulated and LPS stimulated Sdc-1 deficient DC were evaluated in vitro for phenotype and stimulatory capacity in mixed lymphocyte reaction. Sdc-1 deficient T cells were evaluated for proliferative capacity and differentiation in a mixed lymphocyte reaction and a proliferation assay. Allograft survival was evaluated in a fully MHC mismatched heterotopic heart transplant model, with either Sdc-1 deficient donors or recipients. Sdc-1 is expressed on the cell surface of unstimulated and LPS matured DC. Sdc-1 deficiency had no effect on expression of co-stimulatory molecules, cytokine production or T cell stimulatory capacity as compared to WT DC. Sdc-1 expression was not detectable on WT T cells, although intracellular Sdc-1 expression could be demonstrated after ConA activation. Sdc-1 deficient T cells showed reduced proliferation upon DC or ConA stimulation and reduced IL-17 production upon ConA stimulation, compared to WT T cells. Sdc-1 deficiency of either allograft or recipient did not prolong allograft survival. In conclusion, Sdc-1 is expressed on the cell surface of DC, where its absence does not affect DC phenotype or T cell stimulatory capacity. Sdc-1 is intracellularly expressed in ConA activated T cells. Sdc-1 deficiency in T cells results in a reduced proliferative response in vitro, as induced by DC and ConA. Sdc-1 deficiency in donor or recipient does not affect allograft survival.

immunology↗