Molecular landscapes of the hematopoietic niche: single-cell insights and inflammatory signatures in sickle cellanemia

Abstract

Sickle Cell Anemia (SCA) is a complex hematological disorder encompassing dysregulated hematopoiesis andchronic inflammation within the bone marrow. This interdisciplinary project investigates the molecular intricaciesof bone marrow aspirates from three distinct subject groups: healthy donors (control group), chronicallytransfused SCA patients, and hydroxyurea-treated SCA patients (study groups). Leveraging single-cell RNAsequencing on bone marrow-derived mononuclear cells, this study aims to unveil unique gene expression profilesat the single-cell level, employing the Chromium Fixed RNA Profiling technology, which enables comprehensivegene expression measurements in fixed samples, enabling up to 16 uniquely barcoded samples pooled within asingle library construction reaction. Additionally, fluorescence-activated cell sorting will dissect the cellconstitution of the hematopoietic stem cell and immunological compartments. In addition, the proposedmethodology extends beyond transcriptomics to quantifying cytokines and chemokines related to hematopoiesisand inflammation in bone marrow plasma. This integrative approach delineates the dynamic cellular andmolecular interactions governing hematopoiesis and inflammation in SCA. Expected results include theidentification of novel cell subpopulations, dysregulated molecular pathways, and inflammatory signatures specificto SCA. Furthermore, the project seeks to establish correlations between transcriptomic alterations and changesin the hematopoietic niche. This research holds significant relevance for advancing our understanding of SCApathophysiology, providing insights into potential therapeutic targets, and improving the way for personalizedtreatment strategies such as gene therapies. By bridging the gap between single-cell transcriptomics andinflammation profiling, this project contributes to a holistic comprehension of the bone marrow microenvironmentin SCA, fostering new avenues for innovative clinical interventions. (AU)