| 1. |
- Gomez-Cabrero, D, et al.
(författare)
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STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse
- 2019
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 6:1, s. 256-
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Tidskriftsartikel (refereegranskat)abstract
- Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.
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| 2. |
- Reijmers, Rogier M., et al.
(författare)
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Disruption of heparan sulfate proteoglycan conformation perturbs B-cell maturation and APRIL-mediated plasma cell survival
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:23, s. 6162-6171
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Tidskriftsartikel (refereegranskat)abstract
- The development and antigen-dependent differentiation of B lymphocytes are orchestrated by an array of growth factors, cytokines, and chemokines that require tight spatiotemporal regulation. Heparan sulfate proteoglycans specifically bind and regulate the bioavailability of soluble protein ligands, but their role in the immune system has remained largely unexplored. Modification of heparan sulfate by glucuronyl C5-epimerase (Glce) controls heparan sulfate-chain flexibility and thereby affects ligand binding. Here we show that Glce deficiency impairs B-cell maturation, resulting in decreased plasma cell numbers and immunoglobulin levels. We demonstrate that C5-epimerase modification of heparan sulfate is critical for binding of a proliferation inducing ligand (APRIL) and that Glce-deficient plasma cells fail to respond to APRIL-mediated survival signals. Our results identify heparan sulfate proteoglycans as novel players in B-cell maturation and differentiation and suggest that heparan sulfate conformation is crucial for recruitment of factors that control plasma cell survival.
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| 3. |
- Reijmers, Rogier M, et al.
(författare)
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Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase
- 2010
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 184:7, s. 3656-3664
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Tidskriftsartikel (refereegranskat)abstract
- The development of lymphoid organs depends on cross talk between hematopoietic cells and mesenchymal stromal cells and on vascularization of the lymphoid primordia. These processes are orchestrated by cytokines, chemokines, and angiogenic factors that require tight spatiotemporal regulation. Heparan sulfate (HS) proteoglycans are molecules designed to specifically bind and regulate the bioactivity of soluble protein ligands. Their binding capacity and specificity are controlled by modification of the HS side chain by HS-modifying enzymes. Although HS proteoglycans have been implicated in the morphogenesis of several organ systems, their role in controlling lymphoid organ development has thus far remained unexplored. In this study, we report that modification of HS by the HS-modifying enzyme glucuronyl C5-epimerase (Glce), which controls HS chain flexibility, is required for proper lymphoid organ development. Glce(-/-) mice show a strongly reduced size of the fetal spleen as well as a spectrum of defects in thymus and lymph node development, ranging from dislocation to complete absence of the organ anlage. Once established, however, the Glce(-/-) primordia recruited lymphocytes and developed normal architectural features. Furthermore, Glce(-/-) lymph node anlagen transplanted into wild-type recipient mice allowed undisturbed lymphocyte maturation. Our results indicate that modification of HS by Glce is required for controlling the activity of molecules that are instructive for early lymphoid tissue morphogenesis but may be dispensable at later developmental stages and for lymphocyte maturation and differentiation.
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