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Mar, 2021;8 (3): nwaa180.

Single-cell transcriptomic landscape of human blood cells.

Xiaowei Xie, Mengyao Liu, Yawen Zhang, Bingrui Wang, Caiying Zhu, Chenchen Wang, Qing Li, Yingying Huo, Jiaojiao Guo, Changlu Xu, Linping Hu, Aiming Pang, Shihui Ma, Lina Wang, Wenbin Cao, Shulian Chen, Qiuling Li, Sudong Zhang, Xueying Zhao, Wen Zhou, Hongbo Luo, Guoguang Zheng, Erlie Jiang, Sizhou Feng, Lixiang Chen, Lihong Shi, Hui Cheng, Sha Hao, Ping Zhu, Tao Cheng
Author Information
  1. Xiaowei Xie: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  2. Mengyao Liu: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  3. Yawen Zhang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  4. Bingrui Wang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  5. Caiying Zhu: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  6. Chenchen Wang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  7. Qing Li: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  8. Yingying Huo: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  9. Jiaojiao Guo: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, China.
  10. Changlu Xu: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  11. Linping Hu: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  12. Aiming Pang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  13. Shihui Ma: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  14. Lina Wang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  15. Wenbin Cao: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  16. Shulian Chen: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  17. Qiuling Li: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  18. Sudong Zhang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  19. Xueying Zhao: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  20. Wen Zhou: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, China.
  21. Hongbo Luo: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  22. Guoguang Zheng: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  23. Erlie Jiang: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  24. Sizhou Feng: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  25. Lixiang Chen: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  26. Lihong Shi: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  27. Hui Cheng: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  28. Sha Hao: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  29. Ping Zhu: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. ORCID
  30. Tao Cheng: State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
PMID: 34691592 DOI: 10.1093/nsr/nwaa180

Abstract

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

Keywords

hematopoietic cells human lncRNAs single-cell RNA-seq transcription factor

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