转录组范围的噪声控制了哺乳动物原生细胞中的血统选择
Hannah H Chang1, Martin Hemberg, Mauricio Barahona
1Vascular Biology Programme, Department of Pathology and Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|May 24, 2008
概括
干细胞中的细胞个性源于缓慢的基因表达波动,而不是随机噪音. 这些转移稳定状态会影响细胞命运的决定,影响造血原生细胞的血统承诺.
科学领域:
- 发育生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 克隆种群中的表型细胞对细胞的变异性可能源于基因表达噪声或稳定变异.
- 非遗传细胞的个性源于哺乳动物细胞中蛋白质水平的缓慢波动,从而产生异质性.
- 这种异质性在随机干细胞命运决定中的作用尚不清楚.
研究的目的:
- 调查非遗传细胞个性是否有助于干细胞中随机细胞命运决定.
- 描述小鼠造血原生细胞的克隆群体中基因表达变异的动态.
主要方法:
- 在克隆小鼠血造原始细胞中分析Sca-1 (Ly6a) 表达异常值.
- 对Sca-1异常细胞的转录组分析.
- 使用高斯混合模型对基因表达放松动态的建模.
主要成果:
- 自发Sca-1表达异常值表现出缓慢放松动态 (>1周) 回到父母分布.
- 异常细胞具有明显的转录组,表明非遗传个性.
- 这些独特的转录基因组,虽然是短暂的,但影响了对红状或髓状命运的血统承诺,与特定的转录因子表达相关 (Gata1, PU.1).
结论:
- 基因表达中的克隆异质性反映了转录组的转基因稳定状态,而不是独立的基因噪声.
- 这些缓慢波动的,独特的细胞状态控制多能原始细胞的可逆原始化,用于随机细胞命运决定.
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