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在Nipbl^+/-小鼠胚胎中的胃化阶段基因表达预示着综合征性出生缺陷的发展

Stephenson Chea^1,2, Jesse Kreger³, Martha E Lopez-Burks^1,2

¹Department of Developmental and Cell Biology, School of Biological Sciences, University of California Irvine, Irvine, CA 92697, USA.

Science advances

|March 20, 2024

概括

在动物模型中,乳头缺陷会通过改变中皮层发育和过度表达纳米细胞而导致出生缺陷. 这将Nipbl与康奈莉亚·德朗格综合征的基因表达变化联系在一起.

科学领域:

发展生物学发展生物学
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

动物模型中的乳头缺陷模仿了康奈莉亚·德朗格综合征 (CdLS) 现象型,包括先天缺陷.
之前的研究表明,Nipbl缺乏小鼠的早期心脏发育异常.

研究的目的:

研究Nipbl缺乏对胃化和心脏新月阶段早期胚胎发育的影响.
通过单细胞RNA测序,识别潜在的Nipbl相关发育缺陷的分子机制.

主要方法:

野生类型和Nipbl缺乏的小鼠胚胎的单细胞RNA测序.
在早期胚胎发生过程中对基因表达模式和细胞群动态的分析.

主要成果:

乳头缺乏胚胎的胚胎表现出减少的中皮细胞数量和改变的细胞亚种群比例.
对于中皮系特异性至关重要的基因在Nipbl缺陷胚胎中表达不充分.
纳诺基在所有细菌层中过度表达,导致观察到的基因表达失调.

结论:

乳头缺陷导致中皮系谱规范缺陷和纳米的过度表达.
这些分子变化与在Nipbl缺陷动物和CdLS中观察到的发育异常有关.
这项研究确立了Nipbl,Nanog和出生缺陷之间的机械联系.

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