Professor of Regenerative Medicine
Affiliations: Sanger Institute, Babraham Institute, Cambridge Stem Cell Initiative, DefiniGEN
Understanding the mechanisms controlling cell fate decisions in human development has major importance for regenerative medicine. Indeed the generation of fully functional cell types from stem cells is only achievable by recapitulating a natural succession of cell fate choice. The first event of differentiation of the embryo proper occurs at the stage of gastrulation with the specification of the three primary germ layers ectoderm, mesoderm and endoderm, from which all the cells of adult tissues are derived. The main objective of our group is to define the molecular mechanisms controlling the transition between pluripotency, the endoderm and the hepatic lineages. For that, we use human pluripotent stem cells as in vitro model of development to study the interplays between transcriptional networks, epigenetic modifications and cell cycle which ultimately orchestrate the successive steps of differentiation leading to liver functions. The resulting knowledge allows the development of new culture system to drive differentiation of pluripotent stem cells into almost all the hepatic cells. These cells are then used to model disease in vitro especially metabolic disorders. Overall, our objective is to uncover the mechanisms controlling development and to use the resulting knowledge for generating cell types for clinical applications.
Yiangou L, Ross ADB, Goh KJ, Vallier L. Human Pluripotent Stem Cell-Derived Endoderm for Modeling Development and Clinical Applications. Cell Stem Cell. 2018 Apr 5;22(4):485-499. doi: 10.1016/j.stem.2018.03.016. PMID: 29625066.
Bertero A, Brown S, Madrigal P, Osnato A, Ortmann D, Yiangou L, Kadiwala J, Hubner NC, de Los Mozos IR, Sadée C, Lenaerts AS, Nakanoh S, Grandy R, Farnell E, Ule J, Stunnenberg HG, Mendjan S, Vallier L. The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency. Nature. 2018 Mar 8;555(7695):256-259. doi: 10.1038/nature25784.
Sampaziotis F, Justin AW, Tysoe OC, Sawiak S, Godfrey EM, Upponi SS, Gieseck RL 3rd, de Brito MC, Berntsen NL, Gómez-Vázquez MJ, Ortmann D, Yiangou L, Ross A, Bargehr J, Bertero A, Zonneveld MCF, Pedersen MT, Pawlowski M, Valestrand L, Madrigal P, Georgakopoulos N, Pirmadjid N, Skeldon GM, Casey J, Shu W, Materek PM, Snijders KE, Brown SE, Rimland CA, Simonic I, Davies SE, Jensen KB, Zilbauer M, Gelson WTH, Alexander GJ, Sinha S, Hannan NRF, Wynn TA, Karlsen TH, Melum E, Markaki AE, Saeb-Parsy K*, Vallier L*. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine. 2017 Jul 3. doi: 10.1038/nm.4360. PMID: 28671689. *joint authorship.
Pauklin S, Vallier L. The cell-cycle state of stem cells determines cell fate propensity. Cell. 2013 Sep 26;155(1):135-47. PMID: 24074866 PMCID:PMC3898746
Yusa K*, Rashid ST*, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordóñez A, Hannan N, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA*, Bradley A* and Vallier L* (2011). Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. Oct 12;478(7369):391-4. *joint authorship
Areas of expertise
human pluripotent stem cells, endoderm, differentiation, cell cycle, liver and pancreas.