研究领域
多细胞生命的发育起始于单个受精卵,经过细胞连续分裂和分化,形成多种组织和器官类型,最终发育为成熟个体。虽然生物体各种细胞具有相同的基因组序列,但复杂的转录网络驱动了细胞类型的多样性,并在多细胞生物的发育过程中反映出分化细胞的特定表型。信号转导途径、转录因子和表观遗传调控之间的相互作用决定了细胞的基因表达模式,且一旦生物体发育完全,这种模式通常需要相对稳定地维持。表观遗传是指在基因的DNA序列没有发生改变的情况下,基因表达发生了功能性变化,并最终导致了可遗传表型的产生;因素包括DNA和组蛋白的共价修饰,染色质构象和高级结构,非编码RNA等。表观遗传调控在生物体发育和疾病发生过程中至关重要,其对染色质包装及基因转录活性的改变将影响多能性的建立与维持、细胞命运决定与谱系分化、细胞功能与稳态调节等。虽然多种类型的表观遗传修饰及其相关调节因子已被报道,但其在生理与病理状态下的动态与功能作用仍有待深入研究。我们实验室围绕三个主要内容,即发育过程中的表观遗传编程与重编程,细胞命运决定与转变过程中的表观遗传调控,疾病演变与发展过程中的表观遗传基础;利用前沿的分子生物学方法、成像技术、算法工具、人工智能和胚胎模型等,研究表观遗传及其与发育和疾病的复杂关系。
研究内容
1.表观遗传调控
  • 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.细胞命运决定
  • Zhai et al. Primate gastrulation and early organogenesis at single-cell resolution. Nature (2022)

    PMID: 36517595

  • 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.疾病发生发展
  • 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.新技术和模型
  • Huang et al. Generation of rat forebrain tissues in mice. Cell (2024)

    PMID: 38670071

  • 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

代表论著
  • 1. Huang, J., B. He, X. Yang, X. Long, Y. Wei, L. Li, M. Tang, Y. Gao, Y. Fang, W. Ying, Z. Wang, C. Li, Y. Zhou, S. Li, L. Shi, S. Choi, H. Zhou*, F. Guo*, H. Yang* and J. Wu* (2024). "Generation of rat forebrain tissues in mice. " Cell 187(9): 2129-2142.
  • 2. 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
  • 3. 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.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 7. 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.
  • 8. 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.
  • 9. 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
  • 10. 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.
  • 11. 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
  • 12. 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
  • 13. 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
  • 14. 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.
  • 15. 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.
综述/评述
  • 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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课题组成员

郭帆

研究员/课题组长
guofan@ioz.ac.cn

2008年获得武汉大学学士学位,2014年获得中国科学院大学博士学位,随后在北京大学从事博士后研究工作;2017年3月至2021年4月在四川大学担任研究员、课题组长、博士生导师;2021年5月起任中国科学院动物研究所研究员、干细胞与生殖生物学国家重点实验室PI;研究方向为早期胚胎发育及相关疾病的表观遗传调控,获得国家杰出青年科学基金资助。
  • 胡玉琼(副研究员)
  • 曹羽(实验室主管)
  • 侯昕伶(科研助理)
  • 龙鑫(研究生)
  • 赵东红(研究生)
  • 张瑞丰(研究生)
  • 燕蕊(研究生)
  • 程馨(研究生)
  • 郭敬(研究生)
  • 张前程(研究生)
  • 孙奉圆(研究生)
  • 张帆(研究生)
  • 朱然(研究生)
  • 郭天资(研究生)
博士后出站/毕业人员
  • 钱静静

    博士后 2020-2022
    Cell Research/Cell Discovery科学编辑

联系我们
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  • 电子邮件:caoyu@ioz.ac.cn
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