P-selectin overexpression impairs hematopoietic stem cell homeostasis via inflammatory receptor-mediated proliferation and differentiation.

ABSTRACT: Hematopoietic stem cells (HSC) sustain lifelong blood and immune system homeostasis. This study identifies P-selectin as a pivotal regulator of HSC function under aging and inflammatory stress. We observed pronounced Selp upregulation in aged HSC and inflammatory contexts, which drives excessive proliferation and differentiation while depleting their long-term self-renewal capacity. Using tissue-specific Selp overexpression models, we demonstrate that chronic Selp elevation disrupts HSC polarity, promotes oxidative stress accumulation, and induces genomic instability. Over time, sustained Selp expression leading to LT-HSC exhaustion and impaired hematopoietic reconstitution. Single-cell transcriptomics revealed that Selp enforces a pro-inflammatory transcriptional program in HSC, hyperacti

SUBMITTER: He W 

PROVIDER: S-EPMC12540768 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature