中国病理生理杂志2026，Vol.42Issue(5)：954-962,9.DOI:10.3969/j.issn.1000-4718.2026.05.013
金属还原酶Steap3缺失对小鼠造血系统稳态的作用和机制研究
Role and mechanisms of Steap3 deficiency in maintaining hematopoietic homeostasis in mice
摘要
Abstract
AIM:To investigate the role of the metalloreductase six-transmembrane epithelial antigen of the prostate 3(STEAP3)in maintaining homeostasis of the hematopoietic system in mice.METHODS:A hematopoietic sys-tem-specific Steap3 knockout mouse model(Steap3 fl/fl;Mx-Cre)was used,combined with flow cytometry,to assess the ef-fect of Steap3 deletion on the number and proportion of hematopoietic stem/progenitor cells and mature cells in the mouse bone marrow.A bone marrow transplantation experiment was performed to evaluate the impact of Steap3 deletion on the he-matopoietic reconstitution capacity of hematopoietic stem cells(HSCs).A hematology analyzer was used to assess the number and morphology of mature cells in the peripheral blood of Steap3 knockout mice.RNA-seq was used to analyze the effect of Steap3 deletion on gene transcription.RESULTS:Deletion of Steap3 did not affect the number or hematopoietic reconstitution capacity of HSCs in mice,but it reduced iron content in bone marrow megakaryocyte-erythroid progenitors(MEPs),the common upstream progenitors of both erythroid and platelet lineages,thereby leading to abnormalities in ery-throid and platelet development.Steap3-deficient mice exhibited a differentiation blockade characterized by an increase in erythroid precursor and a decrease in mature erythrocytes.Additionally,Steap3 deletion led to inhibition of platelet activa-tion and reduced platelet aggregation and clot retraction ability in vitro.Transcriptomic analysis revealed that Steap3 dele-tion did not alter the transcriptional profile of HSCs.However,within MEPs,it significantly upregulated genes related to erythroid differentiation while downregulating those involved in platelet development and activation.CONCLUSION:Steap3 deficiency decreases iron content in MEPs,which subsequently results in erythroid differentiation arrest and plate-let dysfunction.关键词
六跨膜前列腺上皮抗原3/巨核-红系祖细胞/红细胞/血小板Key words
six-transmembrane epithelial antigen of the prostate 3/megakaryocyte-erythroid progenitors/erythrocytes/platelets分类
医药卫生引用本文复制引用
林若逸,游婉玲,鞠振宇,陈陟阳..金属还原酶Steap3缺失对小鼠造血系统稳态的作用和机制研究[J].中国病理生理杂志,2026,42(5):954-962,9.基金项目
国家重点研发计划项目(No.2025YFA1805303) （No.2025YFA1805303）
广东省自然科学基金面上项目(No.2026A1515012553) （No.2026A1515012553）
高校青年教师科研创新能力支持项目(No.SRICSPYF-BS2025103) （No.SRICSPYF-BS2025103）
