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从诱导的多能干细胞干细胞中衍生出功能性的早孕期自然杀手细胞亚型

Virginia Chu Cheung^1,2,3, Carly DaCosta^1,2,3, Jennifer Jaimez^1,2,3

¹Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA,92093, USA.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

在整个怀孕和胎盘位置期间,果性自然杀手 (dNK) 细胞功能发生变化. 诱导多能干细胞 (iPSC) 可以模拟这些dNK细胞,帮助研究生殖疾病.

科学领域:

生殖免疫学生殖免疫学
细胞免疫学细胞免疫学
干细胞生物学干细胞生物学

背景情况:

异常的自然杀手 (dNK) 细胞功能涉及到妊娠并发症,如先兆子和早产.
关于dNK细胞异质性的研究主要集中在妊娠早期,使得胎盘dNK功能的理解变得不太清楚.
了解dNK细胞亚型及其在胎盘术语中的区域差异对于生殖健康研究至关重要.

研究的目的:

定义dNK细胞亚型及其在胎盘膜 (CAM) 和基底板 (BP) 的功能特征.
从诱导多能干细胞 (iPSC) 产生功能性dNK样细胞,模仿早期妊娠dNK亚型,开发一种协议.
为了比较来自不同妊娠阶段和胎盘部位的dNK细胞的秘密特征,包括iPSC衍生的dNK细胞.

主要方法:

流细胞计和单细胞转录组学被用来定义dNK亚型的胎盘组织 (CAM和BP).
诱导多能干细胞 (iPSC) 分化为dNK类细胞,TGFβ用于丰富特定亚型 (dNK2) 和诱导标记体表达 (CD9,CD103).
进行了从第一季度的dNK,长期的胎盘dNK (CAM和BP),周围血液NK细胞和iPSC衍生的dNK细胞中的秘密体的蛋白质组分析.

主要成果:

长期的胎盘dNK细胞显示出改变的亚型丰度,与早期妊娠相比,dNK1减少和dNK3增加.
与BP-dNK细胞相比,CAM-dNK细胞表现出较高的dNK2丰度和较低的CD9表达.
被TGFβ治疗的iPSC衍生dNK细胞成功地模仿了第一季度dNK细胞的秘密特征,包括特定蛋白质的丰富.

结论:

在胎盘区域和整个妊娠期间,dNK细胞功能和亚型分布在胎盘区域之间有很大差异.
来自iPSC的dNK细胞为研究dNK细胞异质性和功能提供了可复制的模型,特别是对于早期妊娠次类型.
这些发现为开发用于与dNK细胞功能障碍相关的妊娠并发症的基于细胞的疗法奠定了基础.

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