Publications by authors named "D Bastelica"
Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets.
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- Germline mutations in the ETV6 gene contribute to familial thrombocytopenia and leukemia, affecting how megakaryocytes (cells that produce platelets) develop.
- The study utilized single-cell RNA sequencing to analyze gene expression changes in patient and control CD34 cells, revealing distinct cell differentiation stages during megakaryocyte development.
- Results indicated that ETV6 deficiency disrupts normal megakaryocyte maturation, leading to abnormal cell types and an overactive "ribosome biogenesis" pathway, suggesting potential therapeutic strategies using inhibitors like CX-5461 to improve platelet production.
Antiplatelet therapy through inhibition of the adenosine diphosphate (ADP)/P2Y12 pathway is commonly used in the treatment of acute coronary syndrome (ACS). Although efficient in preventing platelet activation and thrombus formation, it increases the risk of bleeding complications. In patients with ACS receiving platelet aggregation inhibitors, that is, P2Y12 blockers (n = 923), we investigated the relationship between plasma and platelet-associated CD40L levels and bleeding events (n = 71).
View Article and Find Full Text PDFIncreased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes in the setting of T2DM. We evaluated through transcriptomic analysis, differential gene expressions in megakaryocytes from leptin receptor-deficient mice (db/db), exhibiting features of human T2DM, and control mice (db/+).
View Article and Find Full Text PDFBackground/objectives: Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.
Methods: During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.