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TBXT剂量灵敏度和新生的中皮特征与EMT进展在2D人类胃类动物中的脱

Emily A Bulger^1,2, Ivana Muncie-Vasic^1,3, Ashley R G Libby^1,2

¹Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA 94158, USA.

Development (Cambridge, England)

|February 27, 2024

概括

在人类胃化模型中降低了TBXT基因剂量,延迟了表皮细胞到介质细胞的过渡. 这一发现揭示了TBXT水平如何影响细胞运动和人类胚胎生成,独立于中皮体的身份获取.

科学领域:

发展生物学发展生物学
干细胞生物学干细胞生物学
人类胚胎发生

背景情况:

精确调节TBXT表达对于中皮体发育和人类胃流动期间前后轴模式至关重要.
对于TBXT剂量在细胞形态发生和上皮细胞转化为介质细胞转化 (EMT) 中的作用,目前尚不完全理解.

研究的目的:

调查在早期人类胃流动期间降低TBXT剂量的转录和形态后果.
用人类诱导多能干细胞 (hiPSCs) 阐明TBXT水平对EMT进展和中皮分化的影响.

主要方法:

使用来自野生类型,TBXT异合体和TBXT无基因 hiPSCs的二维胃素.
进行了多原子单核RNA测序 (snRNA-seq) 和单核ATAC测序 (snATAC-seq).
在单层格式中将分化的hiPSCs转化为新生的中皮,以评估细胞-细胞粘附.

主要成果:

不同的TBXT剂量并没有阻碍其分化为新生的中皮.
降低的TBXT剂量直接影响了EMT的时间动态,野生类型细胞比TBXT异构和零细胞更早过渡.
TBXT的剂量严重影响了接口蛋白和细胞-细胞粘附的持久性,影响了细胞行为.

结论:

表皮细胞到介质细胞的转变进展可以与早期人类胃流动中的介质皮细胞身份获取分离.
TBXT剂量是人类胚胎发生过程中EMT时间和细胞粘附动态的关键调节者.
这项研究为管理早期人类发育和胃流动的分子机制提供了新的见解.

关键词:

轴的延伸是指轴的延伸.布拉基尤里 (Brachyury) 是一个名为布拉基尤里 (Brachyury) 的机构.在EMT中,EMT是EMT.消化系统的消化胃化物胃化物半层皮质 (Mesoderm) 是一种中层皮质 (Mesoderm).这是 hiPSC.

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