PT - JOURNAL ARTICLE AU - Shujing Lai AU - Yang Xu AU - Wentao Huang AU - Mengmeng Jiang AU - Haide Chen AU - Fang Ye AU - Renying Wang AU - Yunfei Qiu AU - Xinyi Jiang AU - Daosheng Huang AU - Jie Mao AU - Yanwei Li AU - Yingru Lu AU - Jin Xie AU - Qun Fang AU - Tiefeng Li AU - He Huang AU - Xiaoping Han AU - Guoji Guo TI - Mapping Human Hematopoietic Hierarchy at Single Cell Resolution by Microwell-seq AID - 10.1101/127217 DP - 2017 Jan 01 TA - bioRxiv PG - 127217 4099 - http://biorxiv.org/content/early/2017/04/13/127217.short 4100 - http://biorxiv.org/content/early/2017/04/13/127217.full AB - The classical hematopoietic hierarchy, which is mainly built with fluorescence-activated cell sorting (FACS) technology, proves to be inaccurate in recent studies. Single cell RNA-seq (scRNA-seq) analysis provides a solution to overcome the limit of FACS-based cell type definition system for the dissection of complex cellular hierarchy. However, large-scale scRNA-seq is constrained by the throughput and cost of traditional methods. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using extremely simple devices. Using Microwell-seq, we constructed a single-cell resolution transcriptome atlas of human hematopoietic differentiation hierarchy by profiling more than 50,000 single cells throughout adult human hematopoietic system. We found that adult human hematopoietic stem and progenitor cell (HSPC) compartment is dominated by progenitors primed with lineage specific regulators. Our analysis revealed differentiation pathways for each cell types, through which HSPCs directly progress to lineage biased progenitors before differentiation. We propose a revised adult human hematopoietic hierarchy independent of oligopotent progenitors. Our study also demonstrates the broad applicability of Microwell-seq technology.