Scholarlink

<p>Acquired aplastic anemia (AA) serves as a life-threatening hematopoietic disorder with certain morbidity and mortality, which is caused by the immunologic attack-induced lymphocyte destruction of hematopoietic stem/progenitor cells (HSPCs). Longitudinal studies have highlighted the immunodysfunction in the relapse of AA, yet the dissection of natural killer (NK) cell-related pathogenesis remains largely obscure. In this study, we enriched bone marrow blood-derived mononuclear cells (BM-MNCs) for 20 AA patients and 20 healthy donors (HD), and detected the content and immunophenotyping of resident NK cells (rHD-NKs, rAA-NKs) by cell counting and flow cytometry (FCM) assay. Meanwhile, we utilized our well-established “3ILs”-based protocol for the ex vivo induction of expanded NK cells from BM-MNCs (eHD-NKs, eAA-NKs). Besides the cellular phenotyping analyses of eHD-NKs and eAA-NKs, we further compared the cellular viability and the ex vivo cytotoxicity upon tumor cell lines. Finally, with the aid of RNA-sequencing (RNA-SEQ) and bioinformatics analyses, the transcriptomic signatures of eHD-NKs and eAA-NKs were verified, including gene expression profiling and genetic spectrum. Compared to the corresponding HD-NKs (rHD-NKs, eHD-NKs), both the resident and expanded AA-NKs (rAA-NKs, eAA-NKs) were consistently declined in content of total CD3<sup>−</sup>CD56<sup>+</sup> NK cells and the NKp46<sup>+</sup> activated subset, while the CD3<sup>−</sup>CD56<sup>+</sup>CD16<sup>+</sup> NK cells and the relative subsets revealed different trends (e.g., CD25<sup>+</sup>, NKp44<sup>+</sup> NK subsets). Meanwhile, eHD-NKs and eAA-NKs exhibited multifaceted conservations and alterations in gene expression pattern and somatic variation signatures. Overall, these data indicated the similarities and diversities of cellular phenotype and transcriptomic signatures between HD-NKs and AA-NKs in the bone marrow microenvironment. Our findings provided useful references for the bone marrow failure (BMF)-related cytogenetic characterization of AA-NKs, which would facilitate the further development of NK cell-based precise diagnosis and targeted therapeutics for AA in the future.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Uncovering the cytogenetic hallmarks of resident and expanded natural killer cells from patients with acquired aplastic anemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月15日

查看全文
  • Tier Wang,
  • Yuan Meng,
  • Shanshan Zhang,
  • Yuanxin Wang,
  • Wenxia Zhang,
  • Mingyi Xu,
  • Ying Bing,
  • Jiali Huo,
  • Yanxin Huang,
  • Yanian Ren,
  • Jiageng Wang,
  • Keli Ge,
  • Yan Zheng,
  • Wen Gao,
  • Jinfang Sun,
  • Leisheng Zhang

摘要

Acquired aplastic anemia (AA) serves as a life-threatening hematopoietic disorder with certain morbidity and mortality, which is caused by the immunologic attack-induced lymphocyte destruction of hematopoietic stem/progenitor cells (HSPCs). Longitudinal studies have highlighted the immunodysfunction in the relapse of AA, yet the dissection of natural killer (NK) cell-related pathogenesis remains largely obscure. In this study, we enriched bone marrow blood-derived mononuclear cells (BM-MNCs) for 20 AA patients and 20 healthy donors (HD), and detected the content and immunophenotyping of resident NK cells (rHD-NKs, rAA-NKs) by cell counting and flow cytometry (FCM) assay. Meanwhile, we utilized our well-established “3ILs”-based protocol for the ex vivo induction of expanded NK cells from BM-MNCs (eHD-NKs, eAA-NKs). Besides the cellular phenotyping analyses of eHD-NKs and eAA-NKs, we further compared the cellular viability and the ex vivo cytotoxicity upon tumor cell lines. Finally, with the aid of RNA-sequencing (RNA-SEQ) and bioinformatics analyses, the transcriptomic signatures of eHD-NKs and eAA-NKs were verified, including gene expression profiling and genetic spectrum. Compared to the corresponding HD-NKs (rHD-NKs, eHD-NKs), both the resident and expanded AA-NKs (rAA-NKs, eAA-NKs) were consistently declined in content of total CD3−CD56+ NK cells and the NKp46+ activated subset, while the CD3−CD56+CD16+ NK cells and the relative subsets revealed different trends (e.g., CD25+, NKp44+ NK subsets). Meanwhile, eHD-NKs and eAA-NKs exhibited multifaceted conservations and alterations in gene expression pattern and somatic variation signatures. Overall, these data indicated the similarities and diversities of cellular phenotype and transcriptomic signatures between HD-NKs and AA-NKs in the bone marrow microenvironment. Our findings provided useful references for the bone marrow failure (BMF)-related cytogenetic characterization of AA-NKs, which would facilitate the further development of NK cell-based precise diagnosis and targeted therapeutics for AA in the future.