Close
The Leitch group studies the germline cycle in vivo in mammalian embryos, and also in vitro using primary culture systems and pluripotent stem cell models – with the aim of improving our understanding of human development. We are particularly interested in how pluripotency is regulated during the germline cycle and how germ cell development is coordinated with the major germline epigenetic reprogramming events.
We also study how defects in early germline development can lead to severe forms of human infertility or, conversely, the development of germ cell tumours. In particular we are using human pluripotent stem cells to functionally validate findings from genomic investigations undertaken in infertile patients and to establish in vitro disease models of germline dysfunction.
We aim to expand this approach to study a broad range of early developmental disorders in children, with the hope that a better understanding of the underlying biology might lead to better treatment options. This is in keeping with Dr Leitch’s clinical work in the Department of Clinical Genetics at Great Ormond Street Hospital, where he specialises in paediatric rare disease genetics.
Key Publications
2024
Sepulveda-Rincon LP, Wang YF, Whilding C, Ojarikre OA, Turner JMA, Leitch HG. Interrogating the potential of primordial germ cells by injection into early mouse embryos. Developmental Cell 59(6):695-704. DOI: 10.1016/j.devcel.2024.01.022
2024
Shah P, Hill R, Dion C, Clark S, Willems J, Abakir A, Arends M, Reik W, Leitch HG, Garaycoechea JI, Crossan G Primordial germ cell DNA demethylation and development require DNA translesion synthesis. Nature Communications 15, 3734. DOI: 10.1038/s41467-024-47219-2
2022
Santen GWE, Leitch HG, Cobben J. Gene-Disease Relationship Evidence: A clinical perspective focusing on ultra-rare diseases. Human Mutation 43:1082-1088. DOI: 10.1002/humu.24367
2021
Posfai E, Lanner F, Mulas C, Leitch HG. All models are wrong, but some are useful: establishing standards for stem cell-based embryo models. Stem Cell Reports 16(5):1117-1141. DOI: 10.1016/j.stemcr.2021.03.019
2021
Hamazaki N, Kyogoku H, Araki H, Miura F, Horikawa C, Hamada N, Shimamoto S, Hikabe O, Nakashima K, Kitajima T, Ito T, Leitch HG, Hayashi K. Reconstitution of the oocyte transcriptional network with transcription factors. Nature 286, 493-6. DOI: 10.1038/s41586-020-3027-9
2018
Zhang M*, LeitchHG*#, Tang WWC, FestucciaN, Hall-PonseleE, Nichols J, Surani MA, Smith A, Chambers I#. Esrrb complementation rescues development of Nanog-null germ cells. Cell Reports 9;22(2), 332-9. DOI: 10.1016/j.celrep.2017.12.060
2018
Hill PWS, Leitch HG*, Sun Z*, Requena-Torres C*, Amouroux R*, TruferoM, Borkowska M, Terragni J, Vaisvila R, Linnett S, Dharmalingham G, Haberle V, Lenhard B, Zheng Y, Pradhan S, Hajkova P. Epigenetic reprogramming enables the primordial germ cell-to-gonocyte transition in mouse. Nature 555(7696), 392–396. DOI: 10.1038/nature25964
