11 research outputs found
Single Cell RNA Sequencing Identifies HSPG2 and APLNR as Markers of Endothelial Cell Injury in Systemic Sclerosis Skin
Objective: The mechanisms that lead to endothelial cell (EC) injury and propagate the vasculopathy in Systemic Sclerosis (SSc) are not well understood. Using single cell RNA sequencing (scRNA-seq), our goal was to identify EC markers and signature pathways associated with vascular injury in SSc skin.Methods: We implemented single cell sorting and subsequent RNA sequencing of cells isolated from SSc and healthy control skin. We used t-distributed stochastic neighbor embedding (t-SNE) to identify the various cell types. We performed pathway analysis using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA). Finally, we independently verified distinct markers using immunohistochemistry on skin biopsies and qPCR in primary ECs from SSc and healthy skin.Results: By combining the t-SNE analysis with the expression of known EC markers, we positively identified ECs among the sorted cells. Subsequently, we examined the differential expression profile between the ECs from healthy and SSc skin. Using GSEA and IPA analysis, we demonstrated that the SSc endothelial cell expression profile is enriched in processes associated with extracellular matrix generation, negative regulation of angiogenesis and epithelial-to-mesenchymal transition. Two of the top differentially expressed genes, HSPG2 and APLNR, were independently verified using immunohistochemistry staining and real-time qPCR analysis.Conclusion: ScRNA-seq, differential gene expression and pathway analysis revealed that ECs from SSc patients show a discrete pattern of gene expression associated with vascular injury and activation, extracellular matrix generation and negative regulation of angiogenesis. HSPG2 and APLNR were identified as two of the top markers of EC injury in SSc
Digital.CSIC Annual Report 2010
44 páginas, 17 gráficos, 3 fotos.[EN]The repository’s work agenda for 2010 focused on 4 master lines: increased and more varied contents; dinamization of CSIC libraries in this open access project under the auspices of CSIC Libraries Coordination Unit; new services for end-users and new functionalities, and enhanced visibility and cooperation at an international level. All accomplishments considered, the evaluation of the year has been positive, and it has been marked by important developments in all work areas, as this annual report reflects. This Annual report has been prepared by Isabel Bernal and Juan Román Molina.[ES]La agenda de trabajo para 2010 se concentró en 4 líneas guía: más y mayor variedad de contenidos; dinamización de las bibliotecas del CSIC en este proyecto de acceso abierto auspiciado desde la Unidad de Coordinación de Bibliotecas del CSIC; nuevos servicios para usuarios y nuevas funcionalidades tecnológicas y mayor visibilidad y cooperación a nivel internacional. El balance del trabajo realizado es positivo, con importantes avances en todos estos ámbitos, tal y como da cuenta esta memoria anual. La elaboración de la memoria ha corrido a cargo de Isabel Bernal y Juan Román Molina.Peer reviewe
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Protein phosphatase 2A is requisite for the function of regulatory T cells
Immune homeostasis depends on the proper function of regulatory T (Treg) cells. Compromised Treg cell suppressive activity leads to autoimmune disease, graft rejection and promotes anti-tumor immunity. Here we report the previously unrecognized requirement of the serine/threonine phosphatase Protein Phosphatase 2A (PP2A) for the function of Treg cells. Treg cells exhibited high PP2A activity and Treg cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometric analysis revealed that PP2A associates with components of the mTOR pathway and suppresses mTORC1 activity. In the absence of PP2A, Treg cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is requisite for the function of Treg cells and the prevention of autoimmunity