Files
Noorzai_Salma_20772301_2025-2026.pdf.pdf
Open access - Adobe PDF
- 3.12 MB
Details
- Supervisors
- Faculty
- Degree label
- Abstract
- Glutamine uptake constitutes a major regulator of cellular metabolism across hemato-poietic and immune compartments, nonetheless the in vivo role of individual glutamine transporters to blood cell development is still poorly defined. SLC38A2 (SNAT2) is a ubiq-uitously expressed neutral amino acid transporter and displays elevated expression across the hematopoietic stem cell (HSC) compartment, progenitor and differentiated immune cells, suggesting a potential function in hematopoietic balance. This study was designed to assess the consequences of hematopoietic-restricted ablation of Slc38a2 in mice. Using a hematopoietic Vav-Cre Slc38a2 knockout murine model, hematological parame-ters combined with multiparametric flow cytometry were performed to examine stem and progenitor cell compartments, lineage-committed myeloid and lymphoid progenitor populations, together with mature immune cell subsets in bone marrow, thymus and blood circulation. Loss of Slc38a2 produced minor effects on HSCs and multipotent pro-genitor compartments, exhibiting a non-significant shift towards growth of lymphoid-biased LMPPs. Alternatively, committed progenitor populations were significantly im-paired, characterized by increased GMP and CLP proportions, lower MEP populations along with a redistribution of CLPs favoring Ly6D+ B-biased progenitors at the expense of T/NK-biased cells, pointing a skewing of lineage differentiation towards myeloid-granulocytic and B-lymphoid outputs. Despite the alterations in upstream progenitors, T cell development in the thymus large-ly remained unaffected and bulk B, T and NK cell proportions in the periphery showed no major alterations. Nevertheless, naïve CD4+ T cells were markedly reduced accompanied by a corresponding rise in effector-memory CD4+ T cells and peripheral dendritic cell proportions were significantly lower, supporting previous observations suggesting that Slc38a2-depending glutamine transport supports cDC1 survival and function. Overall, Slc38a2 plays a limited role for hematopoietic output in basal conditions yet contributes to the equilibrium of committed progenitor pools as well as the maintenance of DCs and CD4+ T cell subsets and may uncover context-specific metabolic abilities in settings of inflammatory or immune stress.