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在单细胞分辨率下定义人类内耳器官中前感官细胞的发育轨迹

Yoshitomo Ueda¹, Takashi Nakamura^1,2, Jing Nie¹

¹Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Development (Cambridge, England)

|June 29, 2023

概括

人的内耳发育涉及SOX2+前感官细胞分化成头发和支持细胞. 我们的研究显示,支持细胞可能产生II型毛细胞,为听力损失再生提供了洞察力.

科学领域:

发育生物学是发展生物学.
细胞生物学细胞生物学
遗传学是一个遗传学.

背景情况:

内耳的感觉上皮质包含机械敏感的毛细胞和支持细胞,这两种细胞都来自SOX2表达的前感觉细胞.
在人类内耳发育过程中,控制这些细胞系多样化的精确机制尚未完全理解.

研究的目的:

在人类内耳发育过程中阐明SOX2阳性前感官细胞的转录轨迹.
研究导致人类内耳有机体毛细胞和支持细胞的分化途径.

主要方法:

使用CRISPR/Cas9.9建立了一个SOX2-2A-ntdTomato人类胚胎干细胞系.
在内耳器官的SOX2阳性细胞上进行单细胞RNA测序 (分化时间为20-60天).
使用伪时间分析推断发育轨迹.

主要成果:

伪性质分析表明,前庭类型II毛细胞主要来自支持细胞,而不是直接来自双命运的前感官细胞.
基因组丰富分析揭示了不同的分子配置:支持细胞中的离子通道/载体,毛细胞中的Wnt信号.
确定了与细胞命运决定相关的差异性基因表达模式,用于发育内耳细胞.

结论:

提供了人类内耳细胞谱系多样化的精细模型,突出了潜在的支细胞到毛细胞分化路径.
提供了对支持性和毛细胞的不同作用的分子洞察力,有助于理解发育过程.
通过向已识别的基因路径,建议促进听力损失和平衡障碍的头发细胞再生的潜在治疗途径.

关键词:

发展轨迹的发展轨迹头发细胞头发细胞头发细胞人类人类人类人类人类内部耳朵的内部耳朵.感官前置细胞是感官前置细胞.这就是scRNA-seqq.

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