通过共享RNA和染色体单细胞分析确定染色体潜力
Sai Ma1, Bing Zhang2, Lindsay M LaFave3
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology and Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
我们开发了SHARE-seq, 一种测量单细胞染色体可及性和基因表达的方法. 这种技术揭示了染色质变化如何先于细胞命运决定,有助于理解细胞分化.
科学领域:
- 基因组学
- 表观遗传学
- 细胞生物学
背景情况:
- 细胞分化涉及复杂的基因调节,包括染色体的可访问性.
- 了解监管事件的时间顺序至关重要,但由于异步差异化而具有挑战性.
研究的目的:
- 开发一种可扩展的方法,同时测量单细胞中的染色质可访问性和基因表达.
- 研究细胞系结合过程中的染色质变化与基因表达之间的时间关系.
主要方法:
- 同时高通量ATAC和RNA表达与测序 (SHARE-seq) 的开发.
- 使用计算策略来识别 cis 调节相互作用并定义调节色素的域 (DORC).
- 从小鼠皮肤组织中分析了34774个关节形状.
主要成果:
- SHARE-seq可以同时测量单细胞中的染色质可访问性和基因表达.
- 确定了调节性染色体 (DORC) 的区域,并发现它们与超级增强剂重叠.
- 在基因表达过程中,DORC的染色质可访问性变化先于基因表达.
结论:
- 染色体可访问性变化可能会导致细胞对血统的承诺.
- 染色体潜力被计算推断为基因系的测量.
- SHARE-seq是一个多功能平台,用于研究各种组织中的调节电路.
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