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揭示了两个中性粒细胞承诺的原始细胞,这些原始细胞在人类中性粒细胞形成过程中立即先于前兆细胞

Ilaria Signoretto¹, Federica Calzetti¹, Giulia Finotti²

¹Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.

Cellular & molecular immunology

|February 12, 2025

概括

研究人员在人类骨髓中发现了两种新的中性粒细胞发生的原始细胞 (NCP5s和NCP6s),进步了对中性粒细胞形成的理解. 这些细胞在慢性髓性白血病中被扩大,这表明它们在疾病发病过程中起作用.

科学领域:

血液学和免疫学血液学和免疫学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

技术进步显著提高了对骨髓形成的理解,包括使用流细胞计识别各种原始细胞.
早期人类中性质形成的特征已经确定了新的CD66b+原始体,最近的工作定义了中性粒细胞致力于的原始体 (NCPs) 作为最早的中性粒细胞血统前体.

研究的目的:

隔离和表征两种新型中性粒细胞发生的原始细胞 (NCPs),它们位于人类中性粒细胞形成级联中的NCP4之后.
调查这些新确定的NCP的表型,转录,成熟和免疫组织化学特性.
检查血液恶性瘤中NCP和其他中性粒细胞前体的频率,特别是慢性阶段慢性髓性白血病 (CP-CML) 和全身性巨细胞瘤 (SM).

主要方法:

使用流细胞计,侧散光 (SSC) 和CD45RA表达的新型SSC^hiCD66b-CD64dimCD115-NCPs的隔离和特征.
单独的祖先的表型,转录,成熟和免疫组织化学分析.
来自CP-CML和SM患者的骨髓样本的流细胞计分析,以评估原始细胞频率.

主要成果:

确定了两个新的中性粒细胞承诺的原始细胞,SSC^hiCD45RA+NCP5s和SSC^hiCD45RA-NCP6s,在NCP4s和前面的前细胞细胞之后定位.
根据差异化潜力,繁殖能力,转录组和表型特征,NCP5s被发现比NCP6s更不成熟.
在CP-CML患者的骨髓中观察到NCP4s,NCP6s和下游CD45RA阴性中性粒细胞原始体的频率增加,但在MS患者中没有.

结论:

对NCP5s和NCP6s的鉴定完善了对人类中性质形成级联的理解.
在CP-CML中特定中性粒细胞原体的扩张表明它们参与了这种白血病的发病过程.
这些发现有助于更深入地了解正常和恶性血液形成.

关键词:

慢性骨髓性白血病慢性骨髓性白血病在G-CSF中使用.中性粒细胞中性粒细胞.中性粒细胞的祖先.中性构造是一种中性构造.

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