A single-cell survey of cellular hierarchy in acute myeloid leukemia
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(2020) 13:128
RESEARCH
Open Access
A single-cell survey of cellular hierarchy in acute myeloid leukemia Junqing Wu1,4†, Yanyu Xiao1,4†, Jie Sun3†, Huiyu Sun1,4†, Haide Chen1,4†, Yuanyuan Zhu3, Huarui Fu3, Chengxuan Yu1,4, Weigao E.1,4, Shujing Lai1,4, Lifeng Ma1,4, Jiaqi Li1,4, Lijiang Fei1,4, Mengmeng Jiang1,4, Jingjing Wang1,4, Fang Ye1,4, Renying Wang1,4, Ziming Zhou1,4, Guodong Zhang1,4, Tingyue Zhang1,4, Qiong Ding5, Zou Wang5, Sheng Hao5, Lizhen Liu3, Weiyan Zheng3, Jingsong He3, Weijia Huang3, Yungui Wang2, Jin Xie6, Tiefeng Li7, Tao Cheng8,9, Xiaoping Han1,4,10*, He Huang2,3,4,9,10* and Guoji Guo1,2,4,9,10*
Abstract Background: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. Methods: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. Results: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic “cancer attractor” that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. Conclusions: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor. Keywords: Acute myeloid leukemia, Single-cell mRNA sequencing, Microwell-seq, Ribosomal protein, Single-molecule real-time sequencing, Cancer attractor
* Correspondence: [email protected]; [email protected]; [email protected] † Junqing Wu, Yanyu Xiao, Jie Sun, Huiyu Sun and Haide Chen contributed equally to this work. 1 Center for Stem Cell and Regenerative Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China 2 Institute of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provid
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