来自无菌性染色体三组小鼠的生育后代
Takayuki Hirota1, Hiroshi Ohta2,3, Benjamin E Powell1
1Sex Chromosome Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Science (New York, N.Y.)
|August 19, 2017
概括
在细胞重编程过程中失去额外的染色体后, 无菌的小鼠产生正常的后代. 这种三症偏差染色体损失为生育和治疗遗传疾病提供了途径.
科学领域:
- 遗传学
- 发育生物学
- 生殖医学
背景情况:
- 包括性染色体三重症 (XXY,XYY) 在内的无积分症影响了0.1%的人,经常导致不孕.
- 保持正确的染色体数量对于正常发育和健康至关重要.
研究的目的:
- 调查纤维细胞在诱导多能干细胞 (iPSC) 重编程过程中额外的性别染色体的命运.
- 来自三体细胞的iPSC产生功能性雌激细胞的潜力.
主要方法:
- 从三体XXY和XYY小鼠中重新编程成iPSC.
- 在iPSC生成过程中对染色体数量进行分析.
- 状细胞细胞分化成雄性生殖细胞.
- 通过细胞内精子注射评估精子功能和后代生育能力.
主要成果:
- 在重编程过程中,三体性XXY和XY小鼠纤维细胞自发地丢失了额外的性别染色体,产生了euploid XY iPSCs (三体性偏差染色体损失 - TCL).
- 欧体XY细胞可以分化为功能精子,从而产生染色体正常的,肥沃的后代.
- 在源自唐氏综合症小鼠模型和人类三性纤维细胞的iPSC中也观察到TCL,这表明其适用性更广泛.
结论:
- 在iPSC重编程过程中发生的三胞胎偏差染色体损失提供了一种新的策略,可以从无胞胎细胞中生成欧类细胞.
- 这种方法有很大的潜力克服与性染色体异位症和其他三体状况相关的不孕症.
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