Intro
The development of multicellular organisms commences with a single fertilized egg. The fertilized egg undergoes continuous cell division and differentiation, resulting in the formation of various tissue and organ types that eventually develop into a mature organism. Despite having the same genomic sequence, cells in an organism exhibit different phenotypes due to the complex transcriptional networks that drive cell type diversity during development. The interactions between signaling pathways, transcription factors, and epigenetic regulation determine the gene expression pattern of cells, which typically needs to remain stable after the organism has fully developed. Epigenetics refers to functional changes in gene expression that occur without altering the DNA sequence, leading to the production of heritable phenotypes. Epigenetic regulation plays a critical role in organism development and disease occurrence, and changes in chromatin packaging and gene transcriptional activity can affect pluripotency establishment and maintenance, cell fate determination and lineage commitment, cell function and homeostatic regulation, among others. Although various types of epigenetic modifications and their regulatory factors have been reported, their dynamics and functional roles in physiological and pathological states still require further investigation. Our lab focuses on three main directions: epigenetic programming and reprogramming during the developmental process, epigenetic regulation during cell fate determination and transition, and the epigenetic basis of disease evolution and development. We are interested in unraveling the intricate relationship between epigenetics, development, and disease with state-of-the-art molecular biology techniques, advanced imaging technologies, algorithmic tools and in vivo models.
Research
1. Epigenetic Programming and Reprogramming during Development
  • Yan et al. Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development. Nat Genet (2023)

    PMID: 36539615

  • Yan et al. Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing. Cell Stem Cell (2021)

    PMID: 33957080

  • Gu et al. Integrative single-cell analysis of transcriptome, DNA methylome and chromatin accessibility in mouse oocytes. Cell Res (2019)

    PMID: 30560925

  • Li et al. Single-cell multi-omics sequencing of human early embryos. Nat Cell Biol (2018)

    PMID: 29915357

  • Guo et al. Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells. Cell Res (2017)

    PMID: 28621329

  • Guo et al. The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell (2015)

    PMID: 26046443

  • Guo et al. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell (2014)

    PMID: 25220291

  • Gu et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature (2011)

    PMID: 21892189

2. Epigenetic Regulation in Cell Fate Determination and Transition
  • Chen et al. Integration of single-cell transcriptome and chromatin accessibility of early gonads development among goats, pigs, macaques, and humans. Cell Rep (2022)

    PMID: 36323261

  • Yang et al. Chemical pretreatment activated a plastic state amenable to direct lineage reprogramming. Front Cell Dev Biol (2022)

    PMID: 35399519

  • Yang et al. Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation. Commun Biol (2020)

    PMID: 33128002

3. Epigenetics in Disease Evolution and Development
  • Zhang et al. Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET. Cell Rep Med (2023)

    PMID: 36754052

  • Long et al. Obesity modulates cell-cell interactions during ovarian folliculogenesis. iScience (2022)

    PMID: 35005562

  • Shen et al. Unveiling the heterogeneity of NKT cells in the liver through single cell RNA sequencing. Sci Rep (2020)

    PMID: 33173202

  • Chen et al. Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells. Nat Commun (2018)

    PMID: 30218073

4. Novel Molecular and Cell Biology Techniques
  • Wu et al. An aggregation of human embryonic and trophoblast stem cells reveals the role of trophectoderm on epiblast differentiation. Cell Prolif (2023)

    PMID: 37199067

  • Zhai et al. Neurulation of the cynomolgus monkey embryo achieved from 3D blastocyst culture. Cell (2023)

    PMID: 37172562

  • Qian et al. lsolation of mouse ovarian follicles for single-cell RNA-seq and in vitro culture. STAR Protoc (2022)

    PMID: 35830306

  • Yan et al. Protocol for scChaRM-seq: Simultaneous profiling of gene expression, DNA methylation, and chromatin accessibility in single cells. STAR Protoc (2021)

    PMID: 34849489

  • Zhou et al. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature (2019)

    PMID: 31181567

5. Cell Atlas and Knowledge Bases
  • Zhai et al. Primate gastrulation and early organogenesis at single-cell resolution. Nature (2022)

    PMID: 36517595

Selected Publication
  • 1. Zhai, J., Y. Xu, H. Wan, R. Yan, J. Guo, R. Skory, L. Yan, X. Wu, F. Sun, G. Chen, W. Zhao, K. Yu, W. Li*, F. Guo*, N. Plachta* and H. Wang* (2023). “Neurulation of the cynomolgus monkey embryo achieved from 3D blastocyst culture.” Cell 186 (10): 2078-2091. Cover story
  • 2. Yan, R., X. Cheng, C. Gu, Y. Xu, X. Long, J. Zhai, F. Sun, J. Qian, Y. Du, H. Wang* and F. Guo* (2023). “Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development.” Nature Genetics 55(1): 130-143.
  • 3. Zhang, Q., B. Yao, X. Long, Z. Chen, M. He, Y. Wu, N. Qiao, Z. Ma, Z. Ye, Y. Zhang, S. Yao, Y. Wang, H. Cheng, H. Chen, H. Ye, Y. Wang, Y. Li, J. Chen, Z. Zhang*, F. Guo* and Y. Zhao* (2023). “Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET.” Cell Reports Medicine 4(2): 100934.
  • 4. Zhai, J., J. Guo, H. Wan, L. Qi, L. Liu, Z. Xiao, L. Yan, D. A. Schmitz, Y. Xu, D. Yu, X. Wu, W. Zhao, K. Yu, X. Jiang*, F. Guo*, J. Wu* and H. Wang* (2022). “Primate gastrulation and early organogenesis at single-cell resolution.” Nature 612(7941): 732-738.
  • 5. Chen, M., X. Long, M. Chen, F. Hao, J. Kang, N. Wang, Y. Wang, M. Wang, Y. Gao, M. Zhou, L. Duo, X. Zhe, J. He, B. Ren, Y. Zhang, B. Liu, J. Li, Q. Zhang, L. Yan, X. Cui, Y. Wang, Y. Gui, H. Wang, L. Zhu*, D. Liu*, F. Guo* and F. Gao* (2022). “Integration of single-cell transcriptome and chromatin accessibility of early gonads development among goats, pigs, macaques, and humans.” Cell Reports 41(5): 111587.
  • 6. Yan, R., C. Gu*, D. You, Z. Huang, J. Qian, Q. Yang, X. Cheng, L. Zhang, H. Wang, P. Wang* and F. Guo* (2021). “Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing.” Cell Stem Cell 28(9): 1641-1656.
  • 7. Zhou, C., Y. Sun, R. Yan, Y. Liu, E. Zuo, C. Gu, L. Han, Y. Wei, X. Hu, R. Zeng, Y. Li*, H. Zhou*, F. Guo* and H. Yang* (2019). “Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis.” Nature 571(7764): 275-278.
  • 8. Gu, C., S. Liu, Q. Wu, L. Zhang and F. Guo* (2019). “Integrative single-cell analysis of transcriptome, DNA methylome and chromatin accessibility in mouse oocytes.” Cell Research 29(2): 110-123. Cover story
  • 9. Chen, X., J. Zhao, C. Gu, Y. Cui, Y. Dai, G. Song, H. Liu, H. Shen, Y. Liu, Y. Wang, H. Xing, X. Zhu, P. Hao, F. Guo* and X. Liu* (2018). “Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.” Nature Communications 9(1): 3746.
  • 10. Li, L., F. Guo (co-first), Y. Gao, Y. Ren, P. Yuan, L. Yan, R. Li, Y. Lian, J. Li, B. Hu, J. Gao, L. Wen, F. Tang and J. Qiao (2018). “Single-cell multi-omics sequencing of human early embryos.” Nature Cell Biology 20(7): 847-858. Cover Highlight
  • 11. Guo, F.*, L. Li, J. Li, X. Wu, B. Hu, P. Zhu, L. Wen and F. Tang* (2017). “Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells.” Cell Research 27(8): 967-988. Cover story
  • 12. Guo, F., L. Yan, H. Guo, L. Li, B. Hu, Y. Zhao, J. Yong, Y. Hu, X. Wang, Y. Wei, W. Wang, R. Li, J. Yan, X. Zhi, Y. Zhang, H. Jin, W. Zhang, Y. Hou, P. Zhu, J. Li, L. Zhang, S. Liu, Y. Ren, X. Zhu, L. Wen, Y. Q. Gao, F. Tang and J. Qiao (2015). “The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells.” Cell 161(6): 1437-1452. Cover story
  • 13. Guo, F., X. Li, D. Liang, T. Li, P. Zhu, H. Guo, X. Wu, L. Wen, T. P. Gu, B. Hu, C. P. Walsh, J. Li, F. Tang and G. L. Xu (2014). “Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote.” Cell Stem Cell 15(4): 447-459.
  • 14. Gu, T. P., F. Guo (co-first), H. Yang, H. P. Wu, G. F. Xu, W. Liu, Z. G. Xie, L. Shi, X. He, S. G. Jin, K. Iqbal, Y. G. Shi, Z. Deng, P. E. Szabo, G. P. Pfeifer, J. Li and G. L. Xu (2011). “The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.” Nature 477(7366): 606-610.
Reviews/Comments
  • 1. Qian, J*. and F. Guo* (2022). "De novo programming: establishment of epigenome in mammalian oocytes." Biology of Reproduction 107(1): 40-53.
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Members

GUO Fan

Professor/ PI
guofan@ioz.ac.cn

Prof. Fan Guo received his Bachelor’s degree (2008) from Wuhan University and Ph.D. degree (2014) from the University of Chinese Academy of Sciences. He accomplished postdoctoral training (2014-2017) at Biomedical Pioneering Innovation Center of Peking University. From March 2017 to April 2021, he was professor, principal investigator, and doctoral supervisor at Sichuan University. Dr. Guo joined the State Key Laboratory of Stem Cell and Reproductive Biology of Institute of Zoology (CAS) in May 2021. He is currently the principal investigator of the group of reproductive epigenetics.
  • HU Yuqiong(Associate Professor)
  • CAO Yu
    (Lab Manager)
  • HOU Xinling(Research Assistant)
  • LONG Xin(Graduate Student)
  • ZHAO Donghong(Graduate Student)
  • ZHANG Ruifeng(Graduate Student)
  • YAN Rui(Graduate Student)
  • CHENG Xin(Graduate Student)
  • GUO Jing(Graduate Student)
  • ZHANG Qiancheng(Graduate Student)
  • SUN Fengyuan(Graduate Student)
  • ZHANG Fan(Graduate Student)
  • ZHU Ran(Graduate Student)
  • GUO Tianzi(Graduate Student)
Lab Alumni
  • QIAN Jingjing

    Postdoctoral Fellow, 2020-2022
    Cell Research/Cell Discovery, Scientific Editor

Contact
  • CAO Yu
  • Email:caoyu@ioz.ac.cn
  • Address: 1 Beichen West Road, Chaoyang District, Beijing