Research Interests:

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.

Awards and Honors:

Professional Activities:

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Selected Publications:

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. 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. 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. 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 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. 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. 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. 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 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 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 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 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. 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.