Department of Bioengineering, Stanford University, Shriram Center, 443 Via Ortega, Rm 042, Stanford, CA 94305, USA.
Department of Bioengineering, Stanford University, Shriram Center, 443 Via Ortega, Rm 042, Stanford, CA 94305, USA
Development. 2019 Jun 27;146(12):dev170217. doi: 10.1242/dev.170217.
Understanding chromatin regulation holds enormous promise for controlling gene regulation, predicting cellular identity, and developing diagnostics and cellular therapies. However, the dynamic nature of chromatin, together with cell-to-cell heterogeneity in its structure, limits our ability to extract its governing principles. Single cell mapping of chromatin modifications, in conjunction with expression measurements, could help overcome these limitations. Here, we review recent advances in single cell-based measurements of chromatin modifications, including optimization to reduce DNA loss, improved DNA sequencing, barcoding, and antibody engineering. We also highlight several applications of these techniques that have provided insights into cell-type classification, mapping modification co-occurrence and heterogeneity, and monitoring chromatin dynamics.
理解染色质调控对于控制基因调控、预测细胞身份以及开发诊断和细胞疗法具有巨大的潜力。然而，染色质的动态性质以及其结构在细胞间的异质性限制了我们提取其控制原则的能力。染色质修饰的单细胞图谱结合表达测量可以帮助克服这些限制。在这里，我们综述了基于单细胞的染色质修饰测量的最新进展，包括减少 DNA 损失的优化、改进的 DNA 测序、条形码和抗体工程。我们还强调了这些技术的几个应用，这些应用提供了对细胞类型分类、修饰共现和异质性以及监测染色质动力学的深入了解。
