Pan's Laboratory

Guangjin Pan, Ph.D

Principle Investigator

Dr. Guangjin Pan, GIBH Deputy Director-General since September 2016, is currently a full professor of stem cell biology in South China Institute of Stem Cell & Regenerative Medicine.Dr. Pan received his Master degree in Medical Science from Shandong Academy of Medical Science in 2002 and Ph.D in biology from Tsinghua University, Medical School in 2005. Dr. Pan continued his postdoctoral training in James Thomson’s lab in University of Wisconsin-Madison from 2005 to 2010. He was recruited back to GIBH as a principle investigator in 2010. Over the past ten years, Dr. Pan devoted himself to human pluripotent stem cell research and published more than 25 high quality papers as corresponding author or first author in peer reviewed journals, such as Nature Methods, Cell Stem Cell, Cell Research, Stem Cell Reports and so on.

Current Lab Members:

Research Description:

Human pluripotent stem cells (hPSCs), either derived from the early embryo (ES), or induced from somatic cells (iPS), can undergo indefinite self-renewal and differentiate into any cell type in the human body, thus hold great potential for clinical use in regenerative medicine. The research in Pan’s laboratory focus on three parts mainly: 1. To understand the mechanisms by which control the cell fate maintenance and transition of hPSCs. Using hPSCs as a model, the laboratory analyzes how different biological processes such as transcription factors mediated expression profile, signaling pathway, epigenetic change involved in the regulation of cell fate transition; 2. To generate functional neural progenitor cells (NPC) and hematopoietic stem/progenitor cells (HSC/HPC) from hPSCs. The researchers are trying to gain functional HPC and reveal the mechanisms involved in differentiation regulation through an integrated approach using molecular biology, cell biology, epigenetics, genomics, FACS, confocal microscopy and so on. For the hPSCs derived NPCs, after the NPCs are tested for their therapeutic potential in animal models, the final goal of this research is to translate the technology to the re-building of the injured or diseased human brain. 3. To generate highly efficient transgene-free patient’s iPSCs for human disease modeling. The genetic defects in patient derived iPSCs will be corrected and the iPSCs will be differentiated into functional somatic cells for clinical use.

The major achievements of Pan’s laboratory include: 1. Developed an efficient approach to directly convert human urine cells (hUCs) into neural progenitor cells and revealed the role of TGFβ in shaping cell fate during hUCs trans-differentiation; 2. Developed an efficient approach to generate iPSCs from hUCs in a serum-free, virus-free and animal-product free system; 3. Set up an optimized CRISPR/Cas9 platform for rapid hPSCs genome editing efficiently. Based on this platform, the researchers have corrected HBB mutation of β-Thalassemia iPSCs and discovered that polycomb repressive complex 2 is required for maintenance of human embryonic stem cells; 4. Established a system for hematopoietic differentiation of hPSCs and identified CD61 as a specific marker of hemogenic endothelial cells through constructing a GATA2 reporter cell line.

The future research of Pan’s laboratory will focus on the clinical translational research of NPCs; the mechanisms of heterogeneity and cell fate determination during hPSCs differentiation.

Honors:

？   The first class of “Guangdong science and Technology Award”, 3rd laureate, 2010;

？   Outstanding staff award, GIBH, CAS, 2012;

？   The second class of “National Natural Science Awards” , 2nd laureate, 2013;

？   The chief scientist of “National Key Basic Research Program” project of the Ministry of Science and Technology, 2012-2016;

？   Guangdong special support program "scientific and technological innovation leading talent", 2015.

Selected Publications(# first author, *corresponding author）:

1. Wang, W.#, Zhu, Y.#, Huang, K., Shan, Y., Du, J., Dong, X., Ma, P., Wu, P., Zhang, J., Huang, W., Zhang, T., Liao, B., Yao, D., Pan, G*  and Liu, J.* (2017) Suppressing P16Ink4a and P14ARF pathways overcomes apoptosis in individualized human embryonic stem cells. FASEB Journal , Mar;31(3):1130-1140.

2. Huang, K., Gao, J., Du, J., Ma, N., Zhu, Y., Wu, P., Zhang, T., Wang, W., Li, Y., Chen, Q., Hutchins, A., Yang, Z., Zhang,J., Shan, Y., Li, X., Liao, B., Liu, J., Wang, J., 03. Liu, B., Pan, G*. (2016) Generation and analysis of GATA2w/eGFP 2 human ESCs reveal ITGB3/CD61 as a reliable marker for defining hemogenic endothelial cells during hematopoiesis. Stem Cell Reports 7, 1-15.

3. Wang, L., Li, X., Huang, W., Zhou, T., Wang, H., Lin, A., Hutchins, A. P., Su, Z., Chen, Q., Pei, D., and Pan, G*. (2016) TGFβ signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells. Scientific Reports 6, 22484.

4. Li, D., Wang, L., Hou, J., Shen, Q., Chen, Q., Wang, X., Du, J., Cai, X., Shan, Y., Zhang, T., Zhou, T., Shi, X., Li, Y., Zhang, H., and Pan, G*. (2016) Optimized Approaches for Generation of Integration-free iPSCs from Human Urine-Derived Cells with Small Molecules and Autologous Feeder. Stem Cell Reports 6(5), 717-728.

5.Wang, H., Hu, L., Liu, C., Su, Z., Wang, L., Pan, G*., Guo, Y*., He, J*.(2016) 5-HT2 receptors mediate functional modulation of GABAa receptors and inhibitory synaptictransmissions in human iPS-derived neurons. Scientific Reports 6, 20033.

6. Zhou, P., Wu, F., Zhou, T., Cai, X., Zhang, S., Zhang, X., Li, Q., Li, Y., Zheng, Y., Wang, M., Lan, F., Pan, G*., Pei, D., Wei, S*.(2016)Simple and versatile synthetic polydopamine-based surface supports reprogramming of human somatic cells and long-term self-renewal of human pluripotent stem cells under defined conditions. Biomaterials 87, 1-17.

7. Liu, J., Han, Q., Peng, T., Peng, M., Wei, B., Li, D., Wang, X., Yu, S., Yang, J., Cao, S., Huang, K., Hutchins, A. P., Liu, H., Kuang, J., Zhou, Z., Chen, J., Wu, H., Guo, L., Chen, Y., Chen, Y., Li, X., Wu, H., Liao, B., He, W., Song, H., Yao, H., Pan, G., Chen, J*., and Pei, D*. (2015) The oncogene c-Jun impedes somatic cell reprogramming. Nature Cell Biology 17, 856-867.

8. Huang, K., Du, J., Ma, N.,Liu, J, Wu, P., Dong, X., Meng,M., Wang, W., Chen, X., Shi, X.,  Chen, Q., Yang, Z., Chen, S., Zhang, J., Li, Y., Li, W.,Zheng, Y., Cai, J., Li, P., Sun, X., Wang, J., Pei, D., Pan, G*. (2015) GATA2(-/-) human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment.Cell Regeneration 4(1):4.

9. Ma, N#., Shan, Y#., Liao, B#., Kong, G#., Wang, C., Huang, K., Zhang, H., Cai, X., Chen, S., Pei, D., Chen, N*., and Pan, G*. (2015) Factor-induced Reprogramming and Zinc Finger Nuclease-aided Gene Targeting Cause Different Genome Instability in β-Thalassemia Induced Pluripotent Stem Cells (iPSCs). Journal of Biological Chemistry 290, 12079-12089.

10. Huang, K#., Liu, P#., Li, X., Chen, S., Wang, L., Qin, L., Su, Z., Huang, W., Liu, J., Jia, B., Liu, J., Cai, J*., Pei, D*., Pan, G*. (2014) Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response. SCIENCE CHINA-Life Sciences 57,162-170.

11. Jia, B#., Chen, S#., Zhao, Z., Liu, P, Cai, J., Qin, D., Du, J., Wu, C., Chen, Q., Cai, X., Zhang, H., Yu, Y., Pei, D., Zhong, M*., and Pan, G*. (2014) Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells. Life Sciences 108, 22-29 .

12. Liu, J., Wang, L., Su, Z., Wu, W., Cai, X., Li, D., Hou, J., Pei, D., and Pan, G*. (2014) A reciprocal antagonism between miR-376c and TGF-beta signaling regulates neural differentiation of human pluripotent stem cells. FASEB Journal 28, 4642-4656.

13. Wang, L., Wang, L., Huang, W., Su, H., Xue, Y., Su, Z., Liao, B., Wang, H., Bao, X., Qin, D., He, J., Wu, W., So, K. F., Pan, G*., and Pei, D*. (2013) Generation of integration-free neural progenitor cells from cells in human urine. Nature Methods 10, 84-89.

14. Ma, N#., Liao, B#., Zhang, H., Wang, L., Shan, Y., Xue, Y., Huang, K., Chen, S., Zhou, X., Chen, Y., Pei, D., and Pan, G*. (2013) Transcription Activator-like Effector Nuclease (TALEN)-mediated Gene Correction in Integration-free beta-Thalassemia Induced Pluripotent Stem Cells. Journal of Biological Chemistry 288, 34671-34679.

15. Liu, X., Sun, H., Qi, J., Wang, L., He, S., Liu, J., Feng, C., Chen, C., Li, W., Guo, Y., Qin, D., Pan, G., Chen, J., Pei, D*., and Zheng, H*. (2013) Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. Nature Cell Biology 15, 829-NIL_239.

16. Chen, J#., Guo, L#., Zhang, L., Wu, H., Yang, J., Liu, H., Wang, X., Hu, X., Gu, T., Zhou, Z., Liu, J., Liu, J., Wu, H., Mao, S.-Q., Mo, K., Li, Y., Lai, K., Qi, J., Yao, H., Pan, G., Xu, G*., and Pei, D*. (2013) Vitamin C modulates TET1 function during somatic cell reprogramming. Nature Genetics 45, 1504-1509.

17. Pan, G., and Pei, D*. (2012) Order from Chaos: Single Cell Reprogramming in Two Phases. Cell Stem Cell 11, 445-447.

18. Pan, G., Wang, Tao., Yao, H., Pei D.* (2012) Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells. BIOESSAYS 34 472-476.

19. Wang, T., Chen, K., Zeng, X., Yang, J., Wu, Y., Shi, X., Qin, B., Zeng, L., Esteban, Miguel A., Pan, G., and Pei, D*.(2011) The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner. Cell Stem Cell 9, 575-587.

20. Pan, G., Chang, Z., Scholer, H., and Pei, D*. (2002) Stem cell pluripotency and transcription factor Oct4. Cell Research 12, 321-329.

21. Pan, G., and Pei, D*. (2003) Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog. Cell Research 13, 499-502.

22. Pan, G., Qin, B., Liu, N., Scholer, H. R., and Pei, D*. (2004) Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation. Journal of Biological Chemistry 279, 37013-37020.

23. Pan, G., and Pei, D*. (2005) The stem cell pluripotency factor NANOG activates transcription with two unusually potent subdomains at its C terminus. Journal of Biological Chemistry 280, 1401-1407.

24. Pan, G., Li, J., Zhou, Y., Zheng, H., and Pei, D*. (2006) A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. FASEB J 20, 1730-1732.

25. Pan, G.*, and Thomson, J. A. (2007) Nanog and transcriptional networks in embryonic stem cell pluripotency.Cell Research 17, 42-49.

26. Pan, G., Tian, S., Nie, J., Yang, C., Ruotti, V., Wei, H., Jonsdottir, G. A., Stewart, R., and Thomson, J. A*. (2007) Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells. Cell Stem Cell 1, 299-312.

27. Xu, R., Sampsell-Barron, T. L., Gu, F., Root, S., Peck, R. M., Pan, G., Yu, J., Antosiewicz-Bourget, J., Tian, S., Stewart, R., and Thomson, J. A*. (2008) NANOG Is a Direct Target of TGF[beta]/Activin-Mediated SMAD Signaling in Human ESCs. Cell Stem Cell 3, 196-206.

28. Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A., and Kosik, K. S*. (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137, 647-658.

29. Yu, P., Pan, G., Yu, J., and Thomson, James A*. (2011) FGF2 Sustains NANOG and Switches the Outcome of BMP4-Induced Human Embryonic Stem Cell Differentiation. Cell Stem Cell 8, 326-334.