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Kinetic Measurement and Real Time Visualization of Somatic Reprogramming
Published on: July 30, 2016
在细胞重编程期间的单细胞表达分析揭示了早期的随机阶段和晚期的层次阶段
Yosef Buganim1, Dina A Faddah, Albert W Cheng
1The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|September 18, 2012
概括
单细胞分析揭示了细胞重编程期间的关键基因表达动态. 像Esrrb和Utf1这样的新标记物比旧标记物更好地预测诱导多能干细胞 (iPSC) 的进展.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞重编程产生诱导多能干细胞 (iPSCs),但通常只涉及细胞的一小部分.
- 之前的研究分析了大量细胞种群,阻碍了重编程事件的单细胞解决.
研究的目的:
- 在细胞重编程过程中识别单细胞基因表达模式.
- 为了确定能够预测成功生成iPSC的新型标记.
- 阐明控制多能诱导的基因调控网络.
主要方法:
- 在不同重编程阶段对48个基因的单细胞基因表达概况.
- 在早期和晚期重编程阶段之间对基因表达模式的比较分析.
- 确定关键的转录因子及其等级关系.
主要成果:
- 早期重新编程阶段表现出显著的细胞对细胞基因表达变异性,而晚期阶段表现出更均的表达.
- 与Fbxo15,Fgf4和Oct4.4相比,Esrrb,Utf1,Lin28和Dppa2是iPSC命运的优越预测因素.
- 一个分层的基因表达模型出现了,Sox2作为一个上游调节器在后期阶段.
- 下游因素,不包括核心多能性因素,可以激活多能性电路.
结论:
- 单细胞分析为细胞重编程的异质性和动态提供了关键的见解.
- 新型基因表达标记可以提高iPSC生成的效率和预测.
- 一个分层的基因调节网络,独立于Oct4,Sox2,Klf4,c-Myc和Nanog,驱动多能诱导.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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