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Jinyong WANG, Ph. D., Professor

Blood & Immune Cell Regeneration


Staff:Jingyong WANG, Tongjie WANG, Yanping ZHU, Lijuan LIU
Postdoc: Dehao HUANG, Qi ZHANG, Qitong WENG、Yanhong Liu
Students: Bingyan WU, Huan PENG, Jiapin XIONG, Jianhuan LI, Yao WANG, Xiujuan ZHENG, Yunqing LIN, Zhiqian WANG, Ziyun XIAO, Fan ZHANG, Jiaxin WU
 

Regenerated blood and immune cells from pluripotent stem cells (PSCs) are new-style drugs of cell therapy due to the features of precise gene pre-editing, unlimited source, off the shelf, and universal application.

Our group mainly focus on the regeneration of blood & immune cells from PSCs. The main research contents include:

Blood & Immune Cell Regeneration

1. Pluripotent Stem cell and hematopoietic stem/progenitor cell regeneration

Based on the lineage differentiation principle of pluripotent stem cells (ESC/iPSC) and gene editing technique, transplantable hematopoietic stem/progenitor cells are induced from PSCs, to explore alternative cell sources for traditional bone marrow transplantation, and to achieve the purpose of treating tumors, genetic diseases, viral infections, organ degeneration and senescence, pathological inflammation, etc.

2. Pluripotent stem cells and immune cell regeneration (T, B, NK and other immune cells)

Based on the lineage differentiation principle of pluripotent stem cells (ESC/iPSC) and gene editing approaches, we successfully obtained transplantable lymphocyte progenitors, which gave rise to functional terminal B, T, and NK lymphocytes in vivo after transplantation. The derived cell products are and will be evaluated in clinical trials for treating related diseases.



Figure 1. Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells (https://doi.org/10.1016/j.stemcr.2023.01.009)



Figure 2. Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells（https://www.nature.com/articles/s41421-022-00467-2）



Figure 3. Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes (https://www.nature.com/articles/s41590-018-0046-x)



Figure 4. Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors (https://www.nature.com/articles/s41422-019-0251-7)



Figure 5. Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment (https://www.nature.com/articles/s41375-020-0775-3)

 

 

Plain english:
Current interests in my laboratory include: induction of immune and blood cells from pluripotent stem cells, development of cell therapy and anti-tumor research using regenerated cells.

 

Selected publications:

  1. Peng, H., Y. Lin, F. Hu, C. Lv, B. Wu, Q. Weng, L. Liu, C. Xia, X. Liu, Y. Zhao, Q. Zhang, Y. Geng, M. Zhang and J. Wang (2023). "Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells." Stem Cell Reports.
  2. Wu, B., Q. Zhang, P. Hong, L. Liu, H. Peng, C. Xia, T. Wang, Y. Wang, Q. Weng, X. Liu, Y. Geng, J. Wang and H. Wu (2023). "Antigen-specific TCR-T cells from Rag2 gene-deleted pluripotent stem cells impede solid tumour growth in a mouse model." Cell Prolif: e13389.
  3. Xiong, J., Y. Zhao, Y. Lin, L. Chen, Q. Weng, C. Shi, X. Liu, Y. Geng, L. Liu, J. Wang and M. Zhang (2022). "Identification and characterization of innate lymphoid cells generated from pluripotent stem cells." Cell Rep 41(5): 111569.
  4. Huang, D., J. Li, F. Hu, C. Xia, Q. Weng, T. Wang, H. Peng, B. Wu, H. Wu, J. Xiong, Y. Lin, Y. Wang, Q. Zhang, X. Liu, L. Liu, X. Zheng, Y. Geng, X. Du, X. Zhu, L. Wang, J. Hao and J. Wang (2022). "Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells." Cell Discov 8(1): 121.
  5. Huang, D., Q. Zhao, M. Zhang, Q. Weng, Q. Zhang, K. Wang, F. Dong, H. Cheng, F. Hu and J. Wang (2022). "Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell-like cells." Cell Prolif 55(6): e13235.
  6. Yu, B., B. Wu, P. Hong, H. Peng, M. Zhang, Q. Zhang, L. Liu, X. Liu, Y. Geng, J. Wang and Y. Lan (2022). "Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells." Front Cell Dev Biol 10: 859769.
  7. Zhang, Q., B. Wu, Q. Weng, F. Hu, Y. Lin, C. Xia, H. Peng, Y. Wang, X. Liu, L. Liu, J. Xiong, Y. Geng, Y. Zhao, M. Zhang, J. Du and J. Wang (2022). "Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors." Cell Mol Immunol 19(4): 492-503.
  8. Wang, T., C. Xia, Q. Weng, K. Wang, Y. Dong, S. Hao, F. Dong, X. Liu, L. Liu, Y. Geng, Y. Guan, J. Du, T. Cheng, H. Cheng and J. Wang (2022). "Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway." Haematologica 107(1): 154-166.
  9. Zhou, P., C. Xia, T. Wang, Y. Dong, Q. Weng, X. Liu, Y. Geng, J. Wang and J. Du (2021). "Senescent bone marrow microenvironment promotes Nras-mutant leukemia." J Mol Cell Biol 13(1): 72-74.
  10. Lv, C., S. Chen, F. Hu, D. Huang, T. Wang, J. Du, J. Wang and H. Wu (2021). "Pluripotent stem cell-derived CD19-CAR iT cells effectively eradicate B-cell lymphoma in vivo." Cell Mol Immunol 18(3): 773-775.
  11. Xia, C., T. Wang, H. Cheng, Y. Dong, Q. Weng, G. Sun, P. Zhou, K. Wang, X. Liu, Y. Geng, S. Ma, S. Hao, L. Xu, Y. Guan, J. Du, X. Du, Y. Li, X. Zhu, Y. Shi, S. Xu, D. Wang, T. Cheng and J. Wang (2020). "Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment." Leukemia 34(9): 2375-2383.
  12. Guo, R., F. Hu, Q. Weng, C. Lv, H. Wu, L. Liu, Z. Li, Y. Zeng, Z. Bai, M. Zhang, Y. Liu, X. Liu, C. Xia, T. Wang, P. Zhou, K. Wang, Y. Dong, Y. Luo, X. Zhang, Y. Guan, Y. Geng, J. Du, Y. Li, Y. Lan, J. Chen, B. Liu and J. Wang (2020). "Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors." Cell Res 30(1): 21-33.
  13. Guo, R., H. Wu, J. Du and J. Wang (2020). "T cell regeneration: an update on progress and challenges." Blood Sci 2(1): 22-26.
  14. Hu, F., D. Huang, Y. Luo, P. Zhou, C. Lv, K. Wang, Q. Weng, X. Liu, Y. Guan, Y. Geng, J. Du, J. Chen, J. Wang and H. Wu (2020). "Hematopoietic lineage-converted T cells carrying tumor-associated antigen-recognizing TCRs effectively kill tumor cells." J Immunother Cancer 8(2).
  15. Wang, T., C. Lv, F. Hu, L. Liu and J. Wang (2020). "Two-step protocol for regeneration of immunocompetent T cells from mouse pluripotent stem cells." Blood Sci 2(3): 79-88.
  16. Dong, Y., K. Wang, Q. Weng, T. Wang, P. Zhou, X. Liu, Y. Geng, L. Liu, H. Wu, J. Wang and J. Du (2020). "NUP98-HOXA10hd fusion protein sustains multi-lineage haematopoiesis of lineage-committed progenitors in transplant setting." Cell Prolif 53(9): e12885.
  17. Zhang, M., Y. Dong, F. Hu, D. Yang, Q. Zhao, C. Lv, Y. Wang, C. Xia, Q. Weng, X. Liu, C. Li, P. Zhou, T. Wang, Y. Guan, R. Guo, L. Liu, Y. Geng, H. Wu, J. Du, Z. Hu, S. Xu, J. Chen, A. He, B. Liu, D. Wang, Y. G. Yang and J. Wang (2018). "Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes." Nat Immunol 19(3): 279-290.
  18. Weng, Q., F. Hu, M. Zhang, Y. Dong, C. Lv, Y. Wang, X. Liu and J. Wang (2018). "A protocol for generating induced T cells by reprogramming B cells in vivo." Cell Regen 7(1): 7-15.
  19. Wang, T., C. Xia, Y. Dong, X. Chen, J. Wang and J. Du (2018). "Trim27 confers myeloid hematopoiesis competitiveness by up-regulating myeloid master genes." J Leukoc Biol 104(4): 799-809.
  20. Li, X., C. Xia, T. Wang, L. Liu, Q. Zhao, D. Yang, F. Hu, M. Zhang, K. Huang, Y. Geng, Y. Zheng, Y. Guan, H. Wu, X. Chen, G. Pan, J. Chen, J. Du and J. Wang (2017). "Pyrimidoindole derivative UM171 enhances derivation of hematopoietic progenitor cells from human pluripotent stem cells." Stem Cell Res 21: 32-39.
  21. Wang, T., C. Li, C. Xia, Y. Dong, D. Yang, Y. Geng, J. Cai, J. Zhang, X. Zhang and J. Wang (2015). "Oncogenic NRAS hyper-activates multiple pathways in human cord blood stem/progenitor cells and promotes myelomonocytic proliferation in vivo." Am J Transl Res 7(10): 1963-1973.
  22. Chen, X., Q. Zhao, C. Li, Y. Geng, K. Huang, J. Zhang, X. Wang, J. Yang, T. Wang, C. Xia, X. Liu, M. Meng, D. Yang, Y. Zheng, J. Du, X. Zhang, J. Chen, G. Pan and J. Wang (2015). "OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo." Stem Cell Res 15(2): 395-402.
  23. Yang, D., X. Zhang, Y. Dong, X. Liu, T. Wang, X. Wang, Y. Geng, S. Fang, Y. Zheng, X. Chen, J. Chen, G. Pan and J. Wang (2015). "Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo." Cell Cycle 14(4): 612-620.
  24. Wang, J., G. Kong, Y. Liu, J. Du, Y. I. Chang, S. R. Tey, X. Zhang, E. A. Ranheim, M. K. Saba-El-Leil, S. Meloche, A. Damnernsawad, J. Zhang and J. Zhang (2013). "Nras(G12D/+) promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions." Blood 121(26): 5203-5207.
  25. Wang, J., Y. Liu, Z. Li, Z. Wang, L. X. Tan, M. J. Ryu, B. Meline, J. Du, K. H. Young, E. Ranheim, Q. Chang and J. Zhang (2011). "Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner." Blood 118(2): 368-379.
  26. Wang, J., Y. Liu, Z. Li, J. Du, M. J. Ryu, P. R. Taylor, M. D. Fleming, K. H. Young, H. Pitot and J. Zhang (2010). "Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia." Blood 116(26): 5991-6002.