Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Trends Cell Biol. 2022 Mar;32(3):259-271. doi: 10.1016/j.tcb.2021.12.001. Epub 2021 Dec 23.
The epigenome plays a crucial role in modulating the activity of regulatory elements, thereby orchestrating diverse transcriptional programs during embryonic development. Human (h)PSC stepwise differentiation provides an excellent platform for capturing dynamic epigenomic events during lineage transition in human development. Here we discuss how recent technological advances, from epigenomic mapping to targeted perturbation, are providing a more comprehensive appreciation of remodeling of the chromatin landscape during human development with implications for aberrant rewiring in disease. We predict that the continuous innovation of hPSC differentiation methods, epigenome mapping, and CRISPR (clustered regularly interspaced short palindromic repeats) perturbation technologies will allow researchers to build toward not only a comprehensive understanding of the epigenomic mechanisms governing development, but also a highly flexible way to model diseases with opportunities for translation.
表观基因组在调节调控元件的活性方面起着至关重要的作用，从而在胚胎发育过程中协调多样化的转录程序。人类（h）PSC 逐步分化为在人类发育过程中谱系转变期间捕获动态表观遗传事件提供了一个极好的平台。在这里，我们讨论了最近的技术进步，从表观基因组图谱绘制到靶向干扰，如何更全面地了解人类发育过程中染色质景观的重塑及其对疾病中异常重布线的影响。我们预测，hPSC 分化方法、表观基因组图谱绘制和 CRISPR（成簇的规律间隔的短回文重复序列）干扰技术的不断创新将使研究人员不仅能够全面了解控制发育的表观遗传机制，而且还能够以高度灵活的方式对疾病进行建模，从而为转化提供机会。
