在Runx1+血管光滑肌细胞是血液生成干细胞和原始细胞在体内发育的必要条件

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Application of Aorta-gonad-mesonephros Explant Culture System in Developmental Hematopoiesis

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Zaniah N Gonzalez Galofre^1,2, Alastair M Kilpatrick², Madalena Marques²

¹Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK.

Nature communications

|February 23, 2024

概括

血管光滑肌肉细胞前体支持血液发育. 在这些NG2+细胞中删除Runx1会损害胚胎中的造血干细胞 (HSC) 生成和重组潜力.

科学领域:

发展生物学发展生物学
血液形成血液形成血液形成
干细胞生物学干细胞生物学

背景情况:

造血干细胞 (HSC) 对于血液形成至关重要.
支持HSCs的流体细胞与血管光滑肌细胞 (vSMCs) 共享特征.
大动脉 - 淋巴体 - 中 (AGM) 区域的周血管细胞是血液形成的潜在vSMC前体.

研究的目的:

研究NG2+Runx1+周脉细胞在胚胎造血发育中的作用.
为了确定这些细胞是否来自vSMC前体.
了解这些细胞中Runx1删除对HSC生成和功能的影响.

主要方法:

在小鼠AGM区域中识别和表征NG2+Runx1+周脉细胞.
对这些细胞进行转录形状分析,以评估它们的起源.
在NG2+细胞中使用条件淘汰模式对Runx1进行遗传删除.
在体内分析造血发育和HSC复制潜力.
对受影响细胞群体的转录概况.

主要成果:

确定了一个NG2+Runx1+周脉细胞的亚群,具有由硬质瘤衍生的vSMC转录形状.
在NG2+细胞中Runx1的删除在体内损害了胚胎的造血发育.
在AGM区域的细胞周细胞/vSMC,内皮细胞和造血细胞中观察到转录变化.
删除Runx1显著降低了骨髓中的HSC复合潜力.
这些专门的NG2+Runx1+细胞在成年骨髓中不存在.

结论:

NG2+ Runx1+ 周血管细胞代表了一种专门的,胚胎特异的细胞群,对HSC产生至关重要.
这些细胞起源于vSMC前体,并在HSC生成中发挥着至关重要的作用.
Runx1对于这些细胞周细胞的功能至关重要,以支持造血发育和HSC潜力.

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