OpenLB
Open Library of Bioscience
Advanced Search
Science advances
Sep 03, 2021;7 (36): eabi9787.

Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs.

Jun Shen, Yingxi Xu, Shuo Zhang, Shuzhen Lyu, Yingying Huo, Yaoyao Zhu, Kejing Tang, Junli Mou, Xinjie Li, Dixie L Hoyle, Min Wang, Jianxiang Wang, Xin Li, Zack Z Wang, Tao Cheng
Author Information
  1. Jun Shen: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  2. Yingxi Xu: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  3. Shuo Zhang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  4. Shuzhen Lyu: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  5. Yingying Huo: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  6. Yaoyao Zhu: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
  7. Kejing Tang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
  8. Junli Mou: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  9. Xinjie Li: School of Medicine, Sun Yat-sen University, Guangzhou 510006, China. ORCID
  10. Dixie L Hoyle: Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  11. Min Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  12. Jianxiang Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
  13. Xin Li: School of Medicine, Sun Yat-sen University, Guangzhou 510006, China. ORCID
  14. Zack Z Wang: Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ORCID
  15. Tao Cheng: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. ORCID
PMID: 34516916 DOI: 10.1126/sciadv.abi9787

Abstract

Hematopoietic differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic cell and gene regulatory networks but often generates blood cells that lack natural function. Here, we performed extensive single-cell transcriptomic analyses to map fate choices and gene expression patterns during hematopoietic differentiation of hPSCs and showed that oxidative metabolism was dysregulated during in vitro directed differentiation. Applying hypoxic conditions at the stage of endothelial-to-hematopoietic transition in vitro effectively promoted the development of arterial specification programs that governed the generation of hematopoietic progenitor cells (HPCs) with functional T cell potential. Following engineered expression of the anti-CD19 chimeric antigen receptor, the T cells generated from arterial endothelium-primed HPCs inhibited tumor growth both in vitro and in vivo. Collectively, our study provides benchmark datasets as a resource to further understand the origins of human hematopoiesis and represents an advance in guiding in vitro generation of functional T cells for clinical applications.

References

Nature. 2019 Oct;574(7778):365-371 [PMID: 31597962]
Genome Biol. 2020 Jul 1;21(1):157 [PMID: 32611441]
Cell Stem Cell. 2018 Oct 4;23(4):586-598.e8 [PMID: 30290179]
J Clin Invest. 2015 May;125(5):2032-45 [PMID: 25866967]
Cell Cycle. 2011 May 1;10(9):1370-3 [PMID: 21444996]
Haematologica. 2020 Jan 31;105(2):e48-e51 [PMID: 31197070]
Blood. 2012 Jul 12;120(2):314-22 [PMID: 22668850]
Bone Marrow Transplant. 2020 Jun;55(6):1029-1040 [PMID: 31804621]
Cell Metab. 2013 Sep 3;18(3):325-32 [PMID: 23850316]
Nat Biotechnol. 2013 Oct;31(10):928-33 [PMID: 23934177]
Circ Res. 2018 Aug 3;123(4):443-450 [PMID: 29986945]
Nat Commun. 2018 May 8;9(1):1828 [PMID: 29739946]
Nat Commun. 2018 Nov 21;9(1):4906 [PMID: 30464173]
Nat Rev Immunol. 2020 Jan;20(1):55-70 [PMID: 31406325]
Cell Stem Cell. 2018 Dec 6;23(6):850-858.e4 [PMID: 30449714]
Nat Commun. 2019 Jun 3;10(1):2395 [PMID: 31160568]
Stem Cells. 2017 Dec;35(12):2351-2365 [PMID: 29044882]
Cell Prolif. 2021 Apr;54(4):e13012 [PMID: 33656760]
Cell Rep. 2012 Sep 27;2(3):553-67 [PMID: 22981233]
Nature. 2010 Mar 4;464(7285):108-11 [PMID: 20154733]
Nat Commun. 2015 Aug 18;6:8040 [PMID: 26282601]
Nature. 2009 Feb 12;457(7231):887-91 [PMID: 19129762]
Cell Rep. 2012 Dec 27;2(6):1722-35 [PMID: 23219550]
Blood. 2010 Aug 12;116(6):909-14 [PMID: 20453160]
Curr Biol. 2006 Jul 11;16(13):1366-72 [PMID: 16824925]
Adv Sci (Weinh). 2020 Aug 19;7(20):2001019 [PMID: 33101849]
Nat Methods. 2017 May;14(5):521-530 [PMID: 28369043]
Cell Stem Cell. 2010 Dec 3;7(6):718-29 [PMID: 21112566]
Dev Biol. 2018 Feb 15;434(2):292-303 [PMID: 29253505]
Nature. 2014 Jul 17;511(7509):312-8 [PMID: 25030167]
Blood. 2013 Oct 3;122(14):2338-45 [PMID: 23863896]
Cell Rep. 2018 May 22;23(8):2467-2481 [PMID: 29791856]
Blood. 2012 Jun 14;119(24):5706-14 [PMID: 22431573]
Cell Stem Cell. 2013 Jan 3;12(1):31-6 [PMID: 23290135]
Cell Res. 2019 Nov;29(11):881-894 [PMID: 31501518]
Cell Rep. 2017 Apr 4;19(1):10-19 [PMID: 28380349]
J Cell Physiol. 2019 Feb 10;: [PMID: 30740687]
Stem Cells. 2018 Feb;36(2):206-217 [PMID: 29139170]
Cell Stem Cell. 2013 Nov 7;13(5):535-48 [PMID: 24054998]
FEBS Lett. 2019 Dec;593(23):3288-3303 [PMID: 31520530]
Nature. 2010 Mar 4;464(7285):116-20 [PMID: 20154729]
Dev Cell. 2013 Mar 25;24(6):600-11 [PMID: 23537631]
Stem Cell Res Ther. 2018 Dec 7;9(1):340 [PMID: 30526668]
Blood. 2020 Dec 17;136(25):2893-2904 [PMID: 32614947]
Blood. 2014 Jun 12;123(24):3750-9 [PMID: 24782509]
Cell Mol Immunol. 2021 Mar;18(3):773-775 [PMID: 32541834]
Dev Dyn. 2016 Oct;245(10):1011-28 [PMID: 27389484]
Nat Cell Biol. 2015 May;17(5):580-91 [PMID: 25915127]
Nat Commun. 2016 Mar 08;7:10784 [PMID: 26952187]
Science. 2020 Dec 4;370(6521):1186-1191 [PMID: 33273096]
Hum Gene Ther. 2019 Apr;30(4):497-510 [PMID: 30381966]
Cell Stem Cell. 2019 Mar 7;24(3):376-389.e8 [PMID: 30661959]
Stem Cell Reports. 2017 Sep 12;9(3):796-806 [PMID: 28781077]
Oncotarget. 2016 Mar 1;7(9):10638-49 [PMID: 26840021]
Int J Mol Med. 2016 Nov;38(5):1549-1557 [PMID: 27635429]
Nature. 2017 May 25;545(7655):432-438 [PMID: 28514439]
Exp Hematol. 2016 Jul;44(7):540-60 [PMID: 27179622]
J Clin Invest. 2015 Mar 2;125(3):1243-54 [PMID: 25664855]
Stem Cell Reports. 2018 Jul 10;11(1):197-211 [PMID: 29861167]

Grants

  1. R01 DK106109/NIDDK NIH HHS
Journal Article

Word Cloud

Similar Articles

Cited By