OpenLB
Open Library of Bioscience
Advanced Search
Cell discovery
Dec 01, 2020;6 (1): 89.

Characterization and generation of human definitive multipotent hematopoietic stem/progenitor cells.

Yanling Zhu, Tianyu Wang, Jiaming Gu, Ke Huang, Tian Zhang, Zhishuai Zhang, He Liu, Jun Tang, Yuchan Mai, Yanqi Zhang, Yuhang Li, Yashu Feng, Baoqiang Kang, Jinbing Li, Yongli Shan, Qianyu Chen, Jian Zhang, Bing Long, Junwei Wang, Minghui Gao, Di Zhang, Min Zhou, Xiaofen Zhong, Jiekai Chen, Duanqing Pei, Jinfu Nie, Bing Liu, Guangjin Pan
Author Information
  1. Yanling Zhu: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  2. Tianyu Wang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China. ORCID
  3. Jiaming Gu: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China. ORCID
  4. Ke Huang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  5. Tian Zhang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  6. Zhishuai Zhang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  7. He Liu: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  8. Jun Tang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  9. Yuchan Mai: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  10. Yanqi Zhang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  11. Yuhang Li: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  12. Yashu Feng: Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
  13. Baoqiang Kang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  14. Jinbing Li: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  15. Yongli Shan: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  16. Qianyu Chen: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  17. Jian Zhang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  18. Bing Long: Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
  19. Junwei Wang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  20. Minghui Gao: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  21. Di Zhang: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  22. Min Zhou: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  23. Xiaofen Zhong: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  24. Jiekai Chen: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  25. Duanqing Pei: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China. ORCID
  26. Jinfu Nie: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China.
  27. Bing Liu: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China. ORCID
  28. Guangjin Pan: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510530, China. pan_guangjin@gibh.ac.cn. ORCID
PMID: 33298886 DOI: 10.1038/s41421-020-00213-6

Abstract

Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We identify CD44 to specifically discriminate definitive hematopoiesis and generate definitive HSPCs from hESCs. The multipotency of hESCs-derived HSPCs for various blood and immune cells is validated by single-cell clonal assay. Strikingly, these hESCs-derived HSPCs give rise to blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis for generating blood and immune cells for clinical purposes.

References

  1. Nature. 2019 Oct;574(7778):365-371 [PMID: 31597962]
  2. Stem Cell Reports. 2018 Nov 13;11(5):1061-1074 [PMID: 30449319]
  3. Nature. 2010 Mar 4;464(7285):116-20 [PMID: 20154729]
  4. J Biol Chem. 2005 Jun 10;280(23):22385-94 [PMID: 15817467]
  5. Nat Cell Biol. 2015 May;17(5):580-91 [PMID: 25915127]
  6. Science. 2016 Jan 8;351(6269):aab2116 [PMID: 26541609]
  7. Cell Stem Cell. 2007 Dec 13;1(6):635-45 [PMID: 18371405]
  8. Nat Immunol. 2018 Jan;19(1):85-97 [PMID: 29167569]
  9. Cell Stem Cell. 2018 May 3;22(5):627-638 [PMID: 29727678]
  10. Nat Immunol. 2013 Jul;14(7):756-63 [PMID: 23708252]
  11. Immunol Cell Biol. 2016 Mar;94(3):230-5 [PMID: 26526619]
  12. Trends Cell Biol. 2016 Mar;26(3):202-214 [PMID: 26526106]
  13. Nature. 2010 Mar 4;464(7285):108-11 [PMID: 20154733]
  14. Blood. 2006 Sep 15;108(6):2095-105 [PMID: 16757688]
  15. Cell. 2016 Jul 14;166(2):451-467 [PMID: 27419872]
  16. Development. 2004 Feb;131(3):693-702 [PMID: 14729577]
  17. Nat Immunol. 2010 Jul;11(7):585-93 [PMID: 20543838]
  18. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11872-7 [PMID: 12193648]
  19. Cell Rep. 2012 Dec 27;2(6):1722-35 [PMID: 23219550]
  20. Nature. 2018 Jan 24;553(7689):418-426 [PMID: 29364285]
  21. Mol Cell Biol. 1996 Oct;16(10):5634-44 [PMID: 8816476]
  22. Nat Cell Biol. 2017 Apr;19(4):271-281 [PMID: 28319093]
  23. J Leukoc Biol. 2009 Aug;86(2):237-50 [PMID: 19498045]
  24. Nat Biotechnol. 2014 Jun;32(6):554-61 [PMID: 24837661]
  25. Nat Cell Biol. 2016 Jun;18(6):595-606 [PMID: 27183470]
  26. Stem Cell Reports. 2016 Nov 8;7(5):854-868 [PMID: 27746115]
  27. Immunity. 1994 Jul;1(4):291-301 [PMID: 7889417]
  28. Development. 2013 Jun;140(12):2463-7 [PMID: 23715539]
  29. Immunity. 1995 Oct;3(4):459-73 [PMID: 7584137]
  30. Development. 2019 Apr 4;146(7): [PMID: 30890573]
  31. Cell Res. 2019 Nov;29(11):881-894 [PMID: 31501518]
  32. Cell. 2015 Dec 17;163(7):1663-77 [PMID: 26627738]
  33. Cell. 1996 Sep 20;86(6):897-906 [PMID: 8808625]
  34. J Biol Chem. 2019 Sep 13;294(37):13657-13670 [PMID: 31341023]
  35. Cell Stem Cell. 2016 Aug 4;19(2):266-277 [PMID: 27345837]
  36. Blood. 2009 Mar 19;113(12):2655-60 [PMID: 19168785]
  37. Nat Commun. 2018 May 8;9(1):1828 [PMID: 29739946]
  38. Nature. 2009 Feb 12;457(7231):896-900 [PMID: 19212410]
Journal Article
Article has an altmetric score of 11

Word Cloud

Created with Highcharts 10.0.0hematopoiesishumandefinitivecellsHSPCsbloodhematopoieticimmuneearlystem/progenitorgiverisesingle-cellcharacterizeprimitiveembryonichESCs-derivedDefinitivegeneratesmatureremainspoorlydefinedresolvepopulationsearlieststageRNA-seqdistinctmolecularprofilingstemcellhESCdifferentiationdevelopmentidentifyCD44specificallydiscriminategeneratehESCsmultipotencyvariousvalidatedclonalassayStrikinglylymphoidlineagesvivoLastlygene-expressiondynamicsrevealunreportedroleROCK-inhibitionenhancingstudyprovidesprospectunderstandingfirmbasisgeneratingclinicalpurposesCharacterizationgenerationmultipotent

Similar Articles

Cited By