在脏发育过程中,转录因子TCF21对于Foxd1+ stromal祖先通过细胞命运是必要的
bioRxiv : the preprint server for biology
|August 30, 2024
概括
转录因子TCF21对于正常脏发育至关重要. 它在Foxd1+原始体中的丧失破坏了树皮细胞分化,导致异常的发育和先天异常.
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
- 分子遗传学 分子遗传学
背景情况:
- 正常的发育依赖于原生细胞系之间的协调相互作用.
- 福克斯d1+ stromal 先生细胞对于发生是必不可少的,分化成各种细胞类型.
- 控制Foxd1+祖先分化的分子机制尚未完全理解.
研究的目的:
- 调查Tcf21的作用,一个中皮特异性的转录因子,在发育期间的Foxd1+ stromal祖先的命运决定.
主要方法:
- 从胚胎第14.5天 (E14.5) Foxd1脏的32,461个GFP+细胞的单细胞RNA测序 (scRNA-seq) 有或没有Tcf21 (Tcf21-cKO).
- 聚类分析以识别不同的树叶亚群.
- 免疫覆盖以确认细胞变化和空间分布.
主要成果:
- 在对照脏中,确定了六个主要的 stromal 亚群.
- Tcf21的丧失导致了特定层层亚群的显著枯竭,包括骨髓/周血管和收藏管相关的层层.
- 在Tcf21-cKO脏中出现了一种新的Endomucin (Emcn) 表达细胞群,表明血管内皮,与Acta2表达细胞的减少相吻合.
结论:
- Tcf21在指导Foxd1+原始细胞分化到特定的树皮细胞命运中发挥着关键作用.
- 干扰TCF21功能导致脏发育异常,并可能导致先天性脏异常.
- 这些发现提供了对细胞异质性和脏疾病的潜在治疗点的见解.
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