Integrated decoding hematopoiesis and leukemogenesis using single-cell sequencing and its medical implication

作者：Pengfei Qin, Yakun Pang, Wenhong Hou, Ruiqing Fu, Yingchi Zhang, Xuefei Wang, Guofeng Meng, Qifa Liu, Xiaofan Zhu, Ni Hong, Tao Cheng, Wenfei Jin · 发表于：Cell Discovery · 年份：2021 · DOI：10.1038/s41421-020-00223-4 · 被引用次数：53 · 研究领域：Single-cell and spatial transcriptomics、Acute Myeloid Leukemia Research、Cancer Genomics and Diagnostics

Single-cell RNA sequencing provides exciting opportunities to unbiasedly study hematopoiesis. However, our understanding of leukemogenesis was limited due to the high individual differences. Integrated analyses of hematopoiesis and leukemogenesis potentially provides new insights. Here we analyzed ~200,000 single-cell transcriptomes of bone marrow mononuclear cells (BMMCs) and its subsets from 23 clinical samples. We constructed a comprehensive cell atlas as hematopoietic reference. We developed counterpart composite index (CCI; available at GitHub: https://github.com/pengfeeei/cci) to search for the healthy counterpart of each leukemia cell subpopulation, by integrating multiple statistics to map leukemia cells onto reference hematopoietic cells. Interestingly, we found leukemia cell subpopulations from each patient had different healthy counterparts. Analysis showed the trajectories of leukemia cell subpopulations were similar to that of their healthy counterparts, indicating that developmental termination of leukemia initiating cells at different phases leads to different leukemia cell subpopulations thus explained the origin of leukemia heterogeneity. CCI further predicts leukemia subtypes, cellular heterogeneity, and cellular stemness of each leukemia patient. Analyses of leukemia patient at diagnosis, refractory, remission and relapse vividly presented dynamics of cell population during leukemia treatment. CCI analyses showed the healthy counterparts of relapsed leukemi...