Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA, USA.
Nat Commun. 2021 Mar 11;12(1):1583. doi: 10.1038/s41467-021-21810-3.
Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.
急性髓系白血病的研究依赖于 DNA 测序和流式细胞术免疫表型分析，作为疾病特征描述的主要工具。然而，白血病肿瘤异质性使得整合来自单独测量的 DNA 变体和免疫表型变得复杂。在这里，我们介绍了 DAb-seq，这是一种从单个细胞中同时捕获 DNA 基因型和细胞表面表型的高通量技术，可直接对成千上万的细胞中的蛋白质基因组状态进行分析。为了验证该方法，我们对三名白血病患者在多个治疗时间点和疾病复发时的疾病进行了分析。我们观察到复杂的基因型-表型动态变化，说明了疾病过程的微妙性以及不同临床情况下原始细胞基因型和表型之间的不一致程度。我们的结果强调了结合单细胞 DNA 和蛋白质测量以充分描述白血病异质性的重要性。
