University of Exeter Medical School

Dr Ge Guo

Dr Ge Guo

Senior Research Fellow

 G.Guo@exeter.ac.uk

 +44 (0) 1392 72 3042

 Living Systems Institute T02.10

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

My research is focussed on mammalian pluripotent stem cells and cell fate transition during early embryo development. Key research areas in the lab include:

  1.  Understanding the developmental plasticity of human naïve stem cells.
  2.  Modeling early human embryo development ex vivo by reconstruction of embryo structures.
  3.  Establishing pluripotent stem cells from various mammalian species and elucidation of shared and distinct gene regulatory features (collaborative with Professor Austin Smith)

Recently we succeeded in generating human blastoids that closely resemble the natural human embryo  opening up exciting new research possibilities.

Yanagida et al., Naive stem cell blastocyst model captures human embryo lineage segregation    Cell Stem Cell, 2021 (https://pubmed.ncbi.nlm.nih.gov/33957081/)

 We are looking for motivated postdocs and PhD students to study  human naive pluripotent stem cells and  stem cell derived human embryo models. 

Current job opening: postdoctoral research fellow/ associate (https://jobs.exeter.ac.uk  , Job Reference R73730)

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Research

Research interests

My main research is centred on human naïve pluripotency and cell fate transition. During my post-doc research I have developed methods to establish human naïve pluripotent stem cells from embryos, conventional human stem cells and from somatic cells. Importantly,  the human naïve pluripotent stem cells we generated are closely related to resident cells in the early human embryo and are genetically stable. My current research shows that unlike mouse embryonic stem cells, human naïve stem cells have the unique potential to differentiate into all cell types in an embryo including the extra-embryonic lineages.  My research group will continue the study on human naïve pluripotency to understand the developmental plasticity and the underlying regulatory mechanisms. Furthermore, by harnessing the unique extraembryonic differentiation potential we aim to establish a synthetic human blastocyst model. This will enable application of the latest molecular, genetic and biophysical approaches to gain knowledge and understanding of human-specific features of early embryo development. 

Key publications

Guo G*., Stirparo, G.G., Strawbridge, S., Spindlow, D., Yang, J., Clarke, J., Dattani, A., Yanagida, A., Li, M.A., Myers, S., et al. (2021). Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential. Cell Stem Cell, 2020.2002.2004.933812.

Stirparo J.,Smith A. Guo G. Cancer-Related Mutations Are Not Enriched in Naive Human Pluripotent Stem Cells. Cell Stem Cell, 28:164-169.e2, (2021)

Bredenkamp, N., Yang, J., Clarke, J., Stirparo, G.G., von Meyenn, F., Dietmann, S., Baker, D., Drummond, R., Ren, Y., Li, D., Wu, C., Rostovskaya, M., Eminli-Meissner, S., Smith, A., Guo, G., 2019. Wnt inhibition facilitates rna-mediated reprogramming of human somatic cells to naive pluripotency. Stem Cell Reports.

Bredenkamp N, Stirparo G.G., Nichols J, Smith A, and Guo G. The cell-surface marker sushi containing domain 2 facilitates establishment of human naive pluripotent stem cells. Stem Cell Reports 12, 1212-1222 (2019).

Stirparo GG, Boroviak T, Guo G, Nichols J, Smith A, Bertone P. Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human pre-implantation epiblast. Development 145(3):07 Feb 2018

Guo G*, Meyenn F, Rostovskaya M, Clarke J, Dietmann S, Baker D, Sahakyan A, Myers S, Bertone P, Reik W, Plath K, Austin Smith. Epigenetic resetting of human pluripotency. Development. 144: 2748-2763. (2017). *Co-corresponding

Guo G, Meyenn F, Santos F, Chen Y, Reik W, Bertone P, Smith A and Nichols J. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass. Stem Cell Reports 6: 437-46 (2016).

Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, Reik W, Bertone P, Smith A. Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158: 1254-69 (2014).

Research projects

LSI Interdisciplinary PhD Programme Project

Bioengineering naïve stem cell self-organisation to recapitulate the first steps in human embryo development

Supervisor 1: Ge Guo

Supervisor 2: Stefano Pagliara

Project outline

This project is a fusion of stem cell biology with bioengineering and physics of living systems. Human naïve stem cells have the capacity to produce all types of cells including extra embryonic lineages. In this project we aim to control precisely the first differentiation steps so as to produce a synthetic blastocyst comprising three distinct lineages in a specific topological organisation. To achieve this a combination of chemical and environmental cues will be applied to stem cells confined within micro wells in a microfluidic device. This will permitt automated handling of the synthetic blastocysts. The similarity of the synthetic blastocysts to in utero embryos will be evaluated by morphometric and molecular criteria. Further developmental potential will be investigated by extended culture. Finally, the effects of genetic and environmental perturbations on the self-organisation process will be interrogated by real-time imaging and single cell ‘omics.

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Publications

Journal articles

Richards D, Cockerell A, Wright L, Dattani A, Guo G, Smith A, Tsaneva K (2023). Biophysical models of early mammalian embryogenesis. Stem Cell Reports, 18, 26-46.
Strawbridge SE, Clarke J, Guo G, Nichols J (2022). Deriving Human Naïve Embryonic Stem Cell Lines from Donated Supernumerary Embryos Using Physical Distancing and Signal Inhibition. Methods Mol Biol, 2416, 1-12. Abstract.  Author URL.
Dattani A, Huang T, Liddle C, Smith A, Guo G (2022). Suppression of YAP safeguards human naïve pluripotency. Development, 149(24). Abstract.  Author URL.
Dattani A, Guo G (2022). The people behind the papers – Anish Dattani and Ge Guo. Development (Cambridge), 149(24). Abstract.
Stirparo GG, Smith A, Guo G (2021). Cancer-Related Mutations Are Not Enriched in Naive Human Pluripotent Stem Cells. Cell Stem Cell, 28(1), 164-169.e2. Abstract.  Author URL.
Guo G, Stirparo GG, Strawbridge SE, Spindlow D, Yang J, Clarke J, Dattani A, Yanagida A, Li MA, Myers S, et al (2021). Human naive epiblast cells possess unrestricted lineage potential. Cell Stem Cell, 28(6), 1040-1056.e6. Abstract.  Author URL.
Yanagida A, Spindlow D, Nichols J, Dattani A, Smith A, Guo G (2021). Naive stem cell blastocyst model captures human embryo lineage segregation. Cell Stem Cell, 28(6), 1016-1022.e4. Abstract.  Author URL.
Bredenkamp N, Stirparo GG, Nichols J, Smith A, Guo G (2019). The Cell-Surface Marker Sushi Containing Domain 2 Facilitates Establishment of Human Naive Pluripotent Stem Cells. Stem Cell Reports, 12(6), 1212-1222. Abstract.  Author URL.
Bredenkamp N, Yang J, Clarke J, Stirparo GG, von Meyenn F, Dietmann S, Baker D, Drummond R, Ren Y, Li D, et al (2019). Wnt Inhibition Facilitates RNA-Mediated Reprogramming of Human Somatic Cells to Naive Pluripotency. Stem Cell Reports, 13(6), 1083-1098. Abstract.  Author URL.
Guo G, von Meyenn F, Rostovskaya M, Clarke J, Dietmann S, Baker D, Sahakyan A, Myers S, Bertone P, Reik W, et al (2018). Epigenetic resetting of human pluripotency (vol 144, pg 2748, 2017). DEVELOPMENT, 145(8).  Author URL.
Stirparo GG, Boroviak T, Guo G, Nichols J, Smith A, Bertone P (2018). Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human pre-implantation epiblast. DEVELOPMENT, 145(3).  Author URL.
Stirparo GG, Boroviak T, Guo G, Nichols J, Smith A, Bertone P (2018). Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human pre-implantation epiblast (vol 145, dev158501, 2018). DEVELOPMENT, 145(15).  Author URL.
Stirparo GG, Boroviak T, Guo G, Nichols J, Smith A, Bertone P (2018). Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human preimplantation epiblast. Development Abstract.
Guo G, von Meyenn F, Rostovskaya M, Clarke J, Dietmann S, Baker D, Sahakyan A, Myers S, Bertone P, Reik W, et al (2017). Epigenetic resetting of human pluripotency. DEVELOPMENT, 144(15), 2748-2763.  Author URL.
Guo G, von Meyenn F, Santos F, Chen Y, Reik W, Bertone P, Smith A, Nichols J (2016). Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass. STEM CELL REPORTS, 6(4), 437-446.  Author URL.
Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, et al (2015). Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human (vol 158, pg 1254, 2014). CELL, 162(2), 452-453.  Author URL.
Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, et al (2014). Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human. CELL, 158(6), 1254-1269.  Author URL.
Huang Y, Pettitt SJ, Guo G, Liu G, Li MA, Yang F, Bradley A (2012). Isolation of homozygous mutant mouse embryonic stem cells using a dual selection system. NUCLEIC ACIDS RESEARCH, 40(3).  Author URL.
Guo G, Huang Y, Humphreys P, Wang X, Smith A (2011). A <i>PiggyBac</i>-Based Recessive Screening Method to Identify Pluripotency Regulators. PLOS ONE, 6(4).  Author URL.
Wang W, Yang J, Liu H, Lu D, Chen X, Zenonos Z, Campos LS, Rad R, Guo G, Zhang S, et al (2011). Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(45), 18283-18288.  Author URL.
Guo G, Smith A (2010). A genome-wide screen in EpiSCs identifies Nr5a nuclear receptors as potent inducers of ground state pluripotency. DEVELOPMENT, 137(19), 3185-3192.  Author URL.
Yang J, van Oosten AL, Theunissen TW, Guo G, Silva JCR, Smith A (2010). Stat3 Activation is Limiting for Reprogramming to Ground State Pluripotency. CELL STEM CELL, 7(3), 319-328.  Author URL.
Guo G, Yang J, Nichols J, Hall JS, Eyres I, Mansfield W, Smith A (2009). Klf4 reverts developmentally programmed restriction of ground state pluripotency. DEVELOPMENT, 136(7), 1063-1069.  Author URL.
Silva J, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A, et al (2009). Nanog is the Gateway to the Pluripotent Ground State. CELL, 138(4), 722-737.  Author URL.
Hall J, Guo G, Wray J, Eyres I, Nichols J, Grotewold L, Morfopoulou S, Humphreys P, Mansfield W, Walker R, et al (2009). Oct4 and LIF/Stat3 Additively Induce Kruppel Factors to Sustain Embryonic Stem Cell Self-Renewal. CELL STEM CELL, 5(6), 597-609.  Author URL.
Guo G, Wang W, Bradley A (2004). Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells. Nature, 429(6994), 891-895.

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