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Identifier 000397266
Title Gene expression study of hematopoietic stem cells in an experimental model of Systemic Lupus Erythematosus (SLE)
Alternative Title Μελέτη της γονιδιακής έκφρασης των αρχέγονων αιμοποιητικών κυττάρων σε πειραματικό μοντέλο Συστημάτων Ερυθηματώδους Λύκου
Author Γρηγορίου, Μαρία Γ.
Thesis advisor Μπάνος, Α.
Reviewer Μπέρτσιας, Γ.
Μπούμπας, Δ.
Abstract Hematopoietic Stem Cells (HSCs) represent a cell population that gives rise to every lineage of blood cells, including granulocytes, lymphocytes, monocytes and endothelial cells, all of which have been implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE). Our working hypothesis is that the fundamental immune aberrations in SLE –genetic or epigenetic-­‐ may be easier to be traced back to the HSC population. Although HSCs are thought to exist in a dormant state within the bone marrow niche, recent evidence suggests that in lupus mice they may overproliferate due to both intrinsic and extrinsic effects. However, the molecular identity and the contribution of these alterations to lupus remain elusive. We found significantly increased frequencies as well as absolute numbers of HSCs in the BM of lupus NZBxNZW/F1 mice with established disease as compared to young NZBxNZW/F1 mice or to C57/BL6 mice. Bone marrow populations such as hematopoietic stem progenitors cells (HSPCs), lymphoid and myeloid lineages seem to differ in homogeneity depending upon either age or disease, indicating an alteration in HSC potential under inflammatory conditions. Accordingly, serum from F1 young mice promotes healthy HSCs to proliferation and skews their differentiation to myeloid lineage. Global gene expression analysis of HSCs originating from lupus mice revealed 547 differentially expressed (DEGs). These significantly DEGs contain crucial transcription factors for hematopoiesis, HSC function and homeostasis, as well as regulators for immune response during inflammation and autoimmune diseases. These data provide initial insights in the fundamental changes of HSC in lupus within the inflammatory milieu of the disease.
Language English
Subject HSCs
RNA-Seq Autoimmunity
Αιμοποιητικά αρχέγονα κύτταρα
Συστηματικός Ερυθηματώδης Λύκος
Issue date 2015-11-20
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
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