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通过单细胞分析揭示人类骨髓中神经前的发育起源和血统偏好:对再生医学的影响

Zhang Changmeng¹, Wang Hongfei¹, Martin Chi-Hang Cheung²

¹Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Genome medicine

|September 4, 2023

概括

人类骨髓 stromal 细胞 (BMSCs) 具有神经分化潜力,起源于骨干神经峰. 了解它们的转录组动力学可以增强细胞治疗和疾病建模应用.

科学领域:

干细胞生物学干细胞生物学
发育神经科学的发展神经科学.
基因组学就是基因组学.

背景情况:

人类骨髓 stromal 细胞 (BMSCs) 是一个多才多艺的原始细胞群,能够产生神经和中皮细胞类型.
在动物模型中的血统追踪表明,Nestin+ BMSCs起源于骨干神经.
单细胞分析对于识别人类BMSC衍生的神经祖先的发育起源至关重要,用于翻译研究.

研究的目的:

研究人类骨髓 stromal 细胞 (BMSCs) 的发育起源和神经分化潜力.
用单细胞RNA测序来描述BMSC及其神经衍生物的转录基因格局.
确定关键的分子驱动因素和轨迹,以引导BMSC分化向神经系.

主要方法:

使用scRNAseq.进行胚胎和成人骨髓,培养BMSC和BMSC衍生的神经圈的转录形状分析.
综合分析scRNAseq数据以重建差异化轨迹.
用生长因子和信号激动剂对BMSC衍生的神经原始体的功能性表征和差异化途径的操纵.

主要成果:

从集成的scRNAseq数据中确定了不同的神经和骨质分化轨迹.
尼斯+/MKI67+ BMSCs 代表神经分化的起始状态,有可能转向骨质生成.
在神经圈培养条件下,Nestin+/PDGFRA+ BMSCs产生神经前体细胞,在SB4治疗时,BMP4信号影响分化 (Pax6上调,Nestin下调).

结论:

来自骨干神经的人类BMSC是骨髓中神经前代细胞的来源.
阐明BMSC衍生的神经前体的转录动态是提高临床应用的差异化效率和安全性的关键.
这项研究为使用BMSC衍生的神经细胞增强细胞疗法和疾病建模铺平了道路.

关键词:

骨髓 stromal 细胞是骨髓中的细胞.细胞分化的细胞分化.细胞谱系细胞谱系神经峰的神经峰再生医学是一种再生医学.单细胞RNA测序的一个细胞.

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