Totipotency is the ability for a cell to contribute to all embryonic and extra-embryonic lineages, and in the strictest sense, to form a new individual. The zygote and 2-cell stage of mouse embryogenesis are totipotent. Interestingly, totipotent cells were recently shown to emerge spontaneously in mouse embryonic stem cell cultures. The expression of MERVL (mouse ERV with a leucine tRNA primer binding site) repeats marks these spontaneously-emerging totipotent cells. MERVL regulates the expression of many early transcripts in mouse embryogenesis and similarly controls the expression of more than one hundred markers of 2 cell-like cells in culture.
Many groups have studied factors which promote the emergence of totipotent cells in pluripotent cultures. These include transcription factors, epigenetic modifiers, chromatin remodellers, transcription factors, post-translational modifiers, tumour suppressors, splicing factors, microRNAs and proteins involved in intracellular signalling. However, it is as yet unclear what factors are the master regulators of the state and which simply promote its emergence through other factors.
In order to identify the master regulators of the totipotent state and disentangle MERVL reporter activation from totipotency, we propose to map mouse embryonic stem cells as they progress towards totipotency, induced by a shortlist of 35 key inducers. Using 10X genomics single-cell RNA sequencing and trajectory analysis, we plan to identify which factors generate bona-fide totipotent cells. Ultimately, this work will allow the identification of novel inducers of the totipotent state, the understanding of the mechanisms underpinning its emergence and transcription factors and small molecule inhibitors which may enable its generation and maintenance.
Moyra Lawrence was born in Cork, Ireland and graduated from Trinity College Dublin, Ireland. She received her PhD from the University of Cambridge, UK in 2015. She then carried out a postdoc in epigenetics in the IGBMC, Strasbourg, France and Helmholtz Zentrum, Munich, Germany, before returning to Cambridge to work on stem cell-derived megakaryocytes. She joined the Yamamoto lab in 2021 as a JSPS Postdoctoral Fellow.
Human iPS Cells for Clinical Applications and Cellular Products. Moyra Lawrence. Handb Exp Pharmacol, Springer 2023 Mar 25. doi: 10.1007/164_2023_643.
Mapping the biogenesis of forward programmed megakaryocytes from pluripotent stem cells. Moyra Lawrence, Arash Shahsavari, Susanne Bornelov, Thomas Moreau, Rebecca McDonald, Thomas M. Vallance, Katarzyna Kania, Maike Paramor, James Baye, Marion Perrin, Maike Steindel, Paula Jimenez, Christopher Penfold, Irina Mohorianu, Cedric Ghevaert. Science Advances 2022 Feb 16 DOI: 10.1126/sciadv.abj8618
CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythaemia. Cavan Bennett, Moyra Lawrence, Jose A Guerrero, Simon Stritt, Amie K Waller, Yahui Yan, Richard W Mifsud, Jose Ballester-Beltran, Ayesha A. Baig, Annett Mueller, Louisa Mayer, James Warland, Christopher J. Penkett, Parsa Akbari, Thomas Moreau, Amanda L Evans, Souradip Mookerjee, Gary J Hoffman, Kourosh Saeb-Parsy, David Adams, Amber L Couzens, Markus Bender, Wendy Erber, Bernhard Nieswandt, Randy J. Read, Cedric Ghevaert. Blood 2022 Apr 7;139(14):2227-2239. DOI: 10.1182/blood.2021013113
Process analysis of pluripotent stem cell differentiation to megakaryocytes to make platelets applying European GMP. Moyra Lawrence, Amanda Evans, Thomas Moreau, Marta Bagnati, Matthew Smart, Enas Hassan, Jahid Hasan, Monica Pianella, Julie Kerby, Cedric Ghevaert. Npj Regenerative Medicine 2021 May 26. https://doi.org/10.1038/s41536-021-00138-y
Advances in stem cell biology Moyra Lawrence and Cedric Ghevaert. Recent Advances in iPSC-Derived Cell Types. 49-67. Induced Pluripotent Stem Cells – Novel Concepts, Elsevier 2021 Jan. https://doi.org/10.1016/C2019-0-04457-3
Transfer to the clinic: Refining Forward Programming of hPSCs to Megakaryocytes for Platelet Production in Bioreactors. Amanda Evans, Amanda Dalby, Holly Rebecca Foster, Daniel Howard, Amie Waller, Momal Taimoor, Moyra Lawrence, Souradip Mookerjee, Marcus Lehmann, Annie Burton, Jorge Valdez, Joseph Italiano, Thomas Moreau, Cedric Ghevaert. Blood Advances 2021 Apr13. DOI: 10.1182/bloodadvances.2020003236
ZMYM2 inhibits NANOG-mediated reprogramming. Moyra Lawrence, Thorold W. Theunissen, Patrick Lombard, David J. Adams, José C. R. Silva. Wellcome Open Res. 2019, Jun 6; 4:88 https://doi.org/10.12688/wellcomeopenres.15250.1
Using genome editing to engineer universal platelets. Moyra Lawrence, Annett Mueller, Cedric Ghevaert. Emerging Topics in Life Sciences. 2019, Apr 17, ETLS20180153; DOI: 10.1042/ETLS20180153.
Lateral Thinking: How Histone Modifications Regulate Gene Expression. Moyra Lawrence, Sylvain Daujat, Robert Schneider. Trends Genet. 2016 Jan;32(1):42-56. DOI: 10.1016/j.tig.2015.10.007.
NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Yael Costa, Junjun Ding, Thorold W Theunissen, Francesco Faiola, Timothy A Hore, Pavel V Shliaha, Miguel Fidalgo, Arven Saunders, Moyra Lawrence, Sabine Dietmann, Satyabrata Das, Dana N Levasseur, Zhe Li, Mingjiang Xu, Wolf Reik, José C R Silva, Jianlong Wang. Nature. 2013 Mar 21;495(7441):370-4. DOI: 10.1038/nature11925.
Main PI of ASHBi Fusion Grant (2023-2025)
ISSCR Travel and Merit Awards, Boston, June 2023
Best Oral Presentation Award, 3rd Place, CiRA Retreat, Kyoto, Feb 2023
Excellent Poster Award, “Towards Understanding Human Development and Evolution”, Osaka, Japan, Jan 2023
Zhongmei Chen Yong Award for Scientific Excellence, ISSCR San Francisco, USA 2022.
JSPS Postdoctoral Fellowship 2021-2022
Research Associateship, Corpus Christi College, Cambridge, 2017 – 2021
Research grant for clinical translation, DSTL, UK, 2019
Wellcome Trust PhD studentship, Wellcome Trust, UK, 2010-2015
Gold Medal, Trinity College, Dublin, Ireland, 2010
Foundation Scholarship, Trinity College, Dublin, Ireland, 2008
D.C. Pepper Memorial Prize in Chemistry, Trinity College, Dublin, Ireland, 2008
Walter Jones Memorial Prize in Organic Chemistry, Trinity College, Dublin, Ireland, 2008
Henley Memorial Prize in science, Trinity College, Dublin, Ireland, 2007
Roberts Memorial Prize in biology, Trinity College, Dublin, Ireland, 2007
Entrance Exhibition Award, Trinity College Dublin, Ireland, 2006