在染色体马赛克胚胎中,HIF1A介导的途径促进了euploid细胞的存活
Estefania Sanchez-Vasquez1, Marianne E Bronner1, Magdalena Zernicka-Goetz1
1Division of Biology 139-74, California Institute of Technology, Pasadena, United States.
eLife
|October 14, 2025
概括
这项研究揭示了缺氧信号有助于早期胚胎管理染色体错误. 低氧暴露改善了马赛克胚胎中的欧类细胞比例,提供了潜在的生育治疗方法.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 生殖医学 生殖医学
背景情况:
- 人类的生育能力往往是由于早期胚胎的染色体形积分减少.
- 胚胎马赛克,即欧体和无体细胞的混合体,是常见的,但不太了解.
- 胚胎通过哪些机制来管理体积是提高生育能力的关键.
研究的目的:
- 通过使用一种新的小鼠模型,研究胚胎在植入前的发育过程中如何管理形积分.
- 探索缺氧和缺氧诱导因子-1A (HIF1A) 在对染色体错误的反应中的作用.
主要方法:
- 使用Mps1抑制剂AZ3146.6建立了染色体马赛克的小鼠模型.
- 分析了AZ3146对染色体分离,发育潜力和HIF1A/Trp53激活的影响.
- 研究了体外低氧暴露和HIF1A抑制对马赛克胚胎的影响.
主要成果:
- 由于AZ3146诱发了形积分和暂时的HIF1A上调,而没有激活Trp53,显示出比逆转更高的发展潜力.
- 低氧暴露减少了DNA损伤,并在马赛克表皮质体中增加了euploid细胞.
- 抑制HIF1A导致形细胞的比例下降.
结论:
- 缺氧信号在调节胚胎对染色体错误的反应中起着关键作用.
- 这些发现表明缺氧调制是提高人类胚胎马赛克发育潜力的潜在策略.
相关概念视频
Nondisjunction
4.8K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
4.8K
Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
Inheritance of Chromatin Structures
7.3K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.3K
Maintenance of the ES Cell State
2.7K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.7K
Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
Mitogens and the Cell Cycle
7.7K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K


