一个单细胞转录基因指纹的压力过早,不平衡的胚胎干细胞的分化
Ximena L Ruden1,2, Aditi Singh1,3, Teya Marben4
1CS Mott Center/Ob/Gyn Department, Wayne State University (WSU), Detroit, Michigan, USA.
Birth defects research
|November 1, 2024
概括
环境压力,如比醇和视网酸破坏早期胚胎发育. 这可能导致干细胞的早产血统不平衡,可能导致流产和出生缺陷.
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
- 毒理学 毒理学 毒理学
背景情况:
- 流产代表了大量的生命损失,但环境原因仍然不太清楚.
- 胚胎干细胞 (ESC) 在早期发育过程中分化为各种血统,这是围植损失的关键窗口.
- 之前的研究表明,高位和视网酸 (RA) 降低ESC多能性,并促进胚胎外内皮 (XEN) 区分.
研究的目的:
- 调查环境压力因素对培养的天真多能性ESCs的转录学效应.
- 了解超的压力和RA如何影响早期发育中的血统规范.
- 为了将细胞对压力的反应与流产和出生缺陷的潜在机制相关联.
主要方法:
- 大量和单细胞RNA测序 (scRNAseq) 在不同的条件下在两个ESC线上进行.
- 在ESC培养中,暴露于sorbitol,带或不带白血病抑制因子 (LIF) 的视网膜酸 (RA),并与正常分化 (ND) 相比.
- 定量PCR (qPCR) 和基因本体学 (GO) 分析证实了转录组的发现.
主要成果:
- 索比托和RA诱导的2细胞胚胎样 (2CEL) 和XEN血统的亚群,包括原始,表皮和内皮内皮 (VE) 细胞.
- 这些压力因素抑制了形成性多能性,导致与正常差异化相比,血统选择的不平衡.
- 虽然批量RNAseq表明了压力诱导的组织者和胎盘标记物,但scRNAseq在少数聚集在一起的细胞中揭示了这些,模仿了体内概念组织.
结论:
- 过的压力和RA等毒性物质可以在早期发育中诱导过早的血统不平衡.
- 这种社会社会差异化失衡可能是环境诱导流产和出生缺陷的关键机制.
- 了解这些压力反应对于识别生殖功能衰竭的环境风险因素至关重要.
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