Mapping Human Pluripotent Stem Cell-derived Erythroid Differentiation by Single-cell Transcriptome Analysis  

作　　者：Zijuan Xin Wei Zhang Shangjin Gong Junwei Zhu Yanming Li Zhaojun Zhang Xiangdong Fang 

机构地区：[1]CAS Key Laboralory of Genome Science and Information,Beijing Institute of Genomics,Chinese Academy of Sciences/China National Center of Bioinformation,Beijing 100101,China [2]College of Life Sciences,University of Chinese Academy of Sciences,Bejing 100049,China [3]Sino-Danish College,University of Chinese Academy of Sciences,Bejing 100190.China [4]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [5]Bejig Key Laboratory of Genome and Precision Medicine Technologies,Beijing 100101,China

出　　处：《Genomics, Proteomics & Bioinformatics》2021年第3期358-376,共19页基因组蛋白质组与生物信息学报（英文版）

基　　金：This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA 16010602);the National Key R&D Program of China(Grant Nos.2016YFC0901700,2017YFC0907400,and 2018YFC0910700);the National Natural Science Foundation of China(Grant Nos.81670109,81870097,81700097,81700116,and 82070114).

摘　　要：There is an imbalance between the supply and demand of functional red blood cells(RBCs)in clinical applications.This imbalance can be addressed by regenerating RBCs using several in vitro methods.Induced pluripotent stem cells(iPSCs)can handle the low supply of cord blood and the ethical issues in embryonic stem cell research,and provide a promising strategy to eliminate immune rejection.However,no complete single-cell level differentiation pathway exists for the iPSC-derived erythroid differentiation system.In this study,we used iPSC line BC1 to establish a RBC regeneration system.The 10X Genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectory on day 14 of the regeneration system.We observed that iPSC differentiation was not synchronized during embryoid body(EB)culture.The cells(on day 14)mainly consisted of mesodermal and various blood cells,similar to the yolk sac hematopoiesis.We identified six cell classifications and characterized the regulatory transcription factor(TF)networks and cell-cell contacts underlying the system.iPSCs undergo two transformations during the differentiation trajectory,accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes.We identified erythroid cells at different stages,such as burst-forming unit erythroid(BFU-E)and orthochromatic erythroblast(ortho-E)cells,and found that the regulation of TFs(e.g.,TFDP1 and FOXO3)is erythroid-stage specific.Immune erythroid cells were identified in our system.This study provides systematic theoretical guidance for optimizing the iPSC-derived erythroid differentiation system,and this system is a useful model for simulating in vivo hematopoietic development and differentiation.

关 键 词：scRNA-seq IPSC HEMATOPOIESIS ERYTHROPOIESIS Differentiation trajectory 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]