Intro
The development of multicellular life commences with a single fertilized egg, which undergoes continuous cellular division and differentiation, giving rise to a wide array of tissue and organ types, ultimately culminating in the formation of a fully developed individual. Despite sharing the same genome sequence, intricate transcriptional networks orchestrate cellular diversity and manifest distinct phenotypes during the course of multicellular organism development. The interplay between signal transduction pathways, transcription factors, and epigenetic regulation governs gene expression patterns in cells, which typically necessitate stable maintenance once the organism reaches full maturity. Epigenetics encompasses functional alterations in gene expression without changes to the DNA sequence itself, ultimately leading to heritable phenotypic outcomes. Factors contains covalent modifications of DNA and histones, chromatin conformation and higher-order structure dynamics, non-coding RNA molecules among others. Epigenetic regulation assumes a pivotal role in organismal development as well as disease pathogenesis. Changes in chromatin packaging and gene transcriptional activity impact pluripotency establishment and maintenance, cell fate determination and lineage differentiation processes along with cellular function modulation and homeostasis regulation mechanisms. Although numerous types of epigenetic modifications alongside their associated enzymes have been reported thus far; further investigations are warranted to elucidate their dynamic nature as well as functional roles within physiological states or pathological conditions. Utilizing state-of-the-art molecular biology techniques, imaging methods, algorithmic tools, artificial intelligence, and embryonic models, we explore the intricate relationship between epigenetics and its role in both development and disease.
Research
1. Epigenetic regulation
  • Liang et al. Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression. Nat Cell Biol (2024)

    PMID: 39080410

  • 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. Cell fate commitment
  • 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. Disease occurrence and progression
  • 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. New technologies and models
  • 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

Selected Publication
  • 1. Liang D*., R. Yan, X. Long, D. Ji, B. Song, M. Wang, F. Zhang, X. Cheng, F. Sun, R. Zhu, X. Hou, T. Wang, W. Zou, Y. Zhang, Z. Pu, J. Zhang, Z. Zhang, Y. Liu, Y. Hu, X. He*, Y. Cao* and F. Guo* (2024). “Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression.” Nature Cell Biology. Online.
  • 2. 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.
  • 3. 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
  • 4. 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.
  • 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. 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
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.
  • CAO Yu
    (Lab Manager)
  • HOU Xinling(Research Assistant)
  • LONG Xin(Postdoctoral Fellow)
  • 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)
  • XIANG Zeming(Graduate Student)
  • YAN Tong(Graduate Student)
  • LIU Jiayi(Undergraduate Student)
  • QIAO Qijie(Undergraduate 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