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王金勇 研究员

血液与免疫细胞再生研究组

欢迎您的加入血液与免疫细胞再生研究组！
- 工作人员：王金勇、王童洁、朱艳平、刘丽娟
- 博士后：黄德浩、张琪、翁启童、刘艳红
- 博士生：吴冰燕、彭欢、熊佳品、李剑焕、王瑶、郑秀娟、林云轻、王智乾、肖子芸（直博生）；学术型硕士生：张帆、吴嘉欣

 
 

　　多能干细胞来源的再生型血液与免疫细胞，兼具基因编辑和无限来源等特点，有望满足细胞药物在现货型、通用型、可及性等方面的需求，最终惠及更多患者，改善人民健康。

　　研究组主要从事血液与免疫细胞再生研究，主要研究内容包括：

　　1. 干细胞与造血干祖细胞再生

基于多能干细胞(ESC/iPSC)谱系分化原理，结合基因编辑，诱导获得可移植的造血干祖细胞种子，探索代替传统骨髓移植细胞来源，实现治疗肿瘤、遗传病、感染、器官退行衰老、病理炎症等适应症的目的。

　　2. 干细胞与免疫细胞再生（T, B, NK等免疫细胞）

基于多能干细胞（ESC/iPSC)谱系分化原理，结合基因编辑，获得可移植的淋巴细胞祖细胞，模拟淋巴细胞发育微环境，进一步制备成熟的B, T, NK细胞。结合细胞疗法原理，探索治疗肿瘤和相关免疫疾病。



图1. Runx1、Hoxa9、Hoxa10组合诱导多能干细胞定向分化长期再生多谱系血液细胞（https://doi.org/10.1016/j.stemcr.2023.01.009）



图2. 人类多能干细胞诱导再生NK细胞技术示意图（https://www.nature.com/articles/s41421-022-00467-2）



图3. 转录因子Hoxb5体内将B细胞重编程为T细胞，实现体内抗肿瘤(https://www.nature.com/articles/s41590-018-0046-x)



图4. 多能干细胞定向再生T细胞，实现体内抗肿瘤(https://www.nature.com/articles/s41422-019-0251-7)



图5. 间充质干细胞修复骨髓微环境，遏制白血病(https://www.nature.com/articles/s41375-020-0775-3)

 

 

研究内容和目标:
课题组主要从事多能干细胞诱导分化获得可移植的血液以及免疫细胞种子，体外模拟发育微环境获得成熟血液及免疫细胞，探索新型细胞疗法治疗肿瘤等相关疾病。

 

代表性发表论文:

  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.