Language
English
Publication Date
12-1-2024
Journal
Experimental Hematology
DOI
10.1016/j.exphem.2024.104653
PMID
39362577
PMCID
PMC11651051
PubMedCentral® Posted Date
12-1-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
The proinflammatory cytokine interferon-gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, as it is induced upon interferon stimulation and required for interferon-dependent HSC activation. To identify the mechanism by which BST2 promotes interferon-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knock out (KO) of BST2 in a murine model does not disrupt immune cell responses to interferon-inducing mycobacterial infection. Furthermore, intravital imaging studies indicate that BST2 KO does not disrupt localization of HSCs relative to endothelial or osteoblastic niches in the bone marrow. However, using imaging-based flow cytometry, we found that IFNγ treatment shifts the lipid raft polarity of WT but not Bst2−/− hematopoietic stem and progenitor cells (HSPCs). Furthermore, RNAseq analysis, reverse phase protein array and western blot analysis of HSPCs indicate that BST2 promotes ERK1/2 phosphorylation during IFNγ-mediated stress. Overall, we find that BST2 facilitates HSC division by promoting cell polarization and ERK activation, thus elucidating a key mechanism of interferon-dependent HSPC activation. These findings inform future approaches in the treatment of cancer and bone marrow failure.
Keywords
Animals, Hematopoietic Stem Cells, Mice, Mice, Knockout, MAP Kinase Signaling System, Antigens, CD, GPI-Linked Proteins, Interferon-gamma, Membrane Microdomains, Mice, Inbred C57BL, Bone Marrow Stromal Antigen 2
Published Open-Access
yes
Recommended Citation
Florez, Marcus A; Thatavarty, Apoorva; Le, Duy T; et al., "BST2 Facilitates Activation of Hematopoietic Stem Cells Through ERK Signaling" (2024). Faculty and Staff Publications. 4982.
https://digitalcommons.library.tmc.edu/baylor_docs/4982
Included in
Health Services Research Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Microbiology Commons