1. Academic Validation
  2. HAX1 inhibits apoptosis and promotes maturation of neutrophils

HAX1 inhibits apoptosis and promotes maturation of neutrophils

  • Cell Commun Signal. 2025 Jul 21;23(1):349. doi: 10.1186/s12964-025-02353-2.
Hanwei Yue 1 Guiying Shi 1 Jiaming Tang 1 Xinyue Li 1 Lin Bai 2
Affiliations

Affiliations

  • 1 Institute of Laboratory Animal Science, CAMS & PUMC, National Human Diseases Animal Model Resource Center, National Center of Technology Innovation for animal model, Chao-Yang District, Beijing, 100021, China.
  • 2 Institute of Laboratory Animal Science, CAMS & PUMC, National Human Diseases Animal Model Resource Center, National Center of Technology Innovation for animal model, Chao-Yang District, Beijing, 100021, China. bailin49@163.com.
Abstract

As the diverse functions of neutrophils continue to be uncovered, elucidating the molecular mechanisms that regulate their differentiation, development, and Apoptosis has become crucial for overcoming limitations in the treatment of neutrophil-related diseases. Hematopoietic cell-specific protein 1-associated protein X 1 (HAX1), encoded by the primary pathogenic gene of autosomal recessive severe congenital neutropenia, serves as a key target for in-depth exploration of neutrophil function. In the Hax1 myeloid knockout C57BL/6J mice and stably transduced HL-60 cells with HAX1 knockdown that we constructed, our results showed that the differentiation of granulocyte-monocyte precursor cells (GMPs) and the maturation of neutrophils were inhibited, significantly reducing the proportion of myeloid cells and neutrophils in both bone marrow and peripheral blood. In addition, HAX1 deletion disrupted mitochondrial structure and mitochondrial membrane potential in neutrophils and increased the protein levels of B-cell lymphoma 2 (Bcl-2) family members and cleaved Caspase-9. Through RNA Sequencing and mRNA validation, we further demonstrated that HAX1 regulates neutrophil Apoptosis and maturation via the mitochondrial-mediated classical apoptotic pathway and Toll-like Receptor 2 (TLR2)-mediated purine-rich box 1 (PU.1) signaling. This study elucidated the critical role of HAX1 in neutrophil differentiation, maturation, and Apoptosis, providing new targets for research into neutrophil-related diseases.

Keywords

Apoptosis; Cell maturation; HAX1; Neutrophil.

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