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Professor Ludovic Vallier

Research Interests

Human pluripotent stem cells, control of differentiation and disease modeling

Understanding the mechanisms controlling early 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 normal 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 and the endoderm lineage. For that, we use human pluripotent stem cells (hESCs and hIPSCs) as in vitro model of development to study the interplays between transcriptional networks, epigenetic modifications and cell cycle which ultimately orchestrate the earliest step of differentiation. The resulting knowledge allows the development of new culture system to drive differentiation of pluripotent stem cells into pancreatic, hepatic, lung and gut cells. These cells are then used to model disease in vitro and we have a specific focus on metabolic disorders affecting the liver and the pancreas. Furthermore, we are currently investigating how similar mechanisms could regulate adult stem cells self-renewal /differentiation during organ regeneration.

Overall, our objective is to uncover the common mechanisms controlling self-renewal and differentiation in both pluripotent and somatic stem cells.

Keywords

iPSC ; ES (embryonic stem cells) ; stem cells ; regenerative medicine

Key Publications

Please follow the link to PubMed for a full list of publications.

Defining murine organogenesis at single-cell resolution reveals a role for the leukotriene pathway in regulating blood progenitor formation. Ibarra-Soria X, Jawaid W, Pijuan-Sala B, Ladopoulos V, Scialdone A, Jörg DJ, Tyser RCV, Calero-Nieto FJ, Mulas C, Nichols J, Vallier L, Srinivas S, Simons BD, Göttgens B, Marioni JC. Nat Cell Biol. 2018 Feb;20(2):127-134.

Genome editing reveals a role for OCT4 in human embryogenesis. Fogarty NME, McCarthy A, Snijders KE, Powell BE, Kubikova N, Blakeley P, Lea R, Elder K, Wamaitha SE, Kim D, Maciulyte V, Kleinjung J, Kim JS, Wells D, Vallier L, Bertero A, Turner JMA, Niakan KK. Nature. 2017 Oct 5;550(7674):67-73.

Platelet function is modified by common sequence variation in megakaryocyte super enhancers. Petersen R, Lambourne JJ, Javierre BM, Grassi L, Kreuzhuber R, Ruklisa D, Rosa IM, Tomé AR, Elding H, van Geffen JP, Jiang T, Farrow S, Cairns J, Al-Subaie AM, Ashford S, Attwood A, Batista J, Bouman H, Burden F, Choudry FA, Clarke L, Flicek P, Garner SF, Haimel M, Kempster C, Ladopoulos V, Lenaerts AS, Materek PM, McKinney H, Meacham S, Mead D, Nagy M, Penkett CJ, Rendon A, Seyres D, Sun B, Tuna S, van der Weide ME, Wingett SW, Martens JH, Stegle O, Richardson S, Vallier L, Roberts DJ, Freson K, Wernisch L, Stunnenberg HG, Danesh J, Fraser P, Soranzo N, Butterworth AS, Heemskerk JW, Turro E, Spivakov M, Ouwehand WH, Astle WJ, Downes K, Kostadima M, Frontini M. Nat Commun. 2017 Jul 13;8:16058.

Common genetic variation drives molecular heterogeneity in human iPSCs. Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S, Bala S, Bensaddek D, Casale FP, Culley OJ, Danecek P, Faulconbridge A, Harrison PW, Kathuria A, McCarthy D, McCarthy SA, Meleckyte R, Memari Y, Moens N, Soares F, Mann A, Streeter I, Agu CA, Alderton A, Nelson R, Harper S, Patel M, White A, Patel SR, Clarke L, Halai R, Kirton CM, Kolb-Kokocinski A, Beales P, Birney E, Danovi D, Lamond AI, Ouwehand WH, Vallier L, Watt FM, Durbin R, Stegle O, Gaffney DJ. Nature. 2017 Jun 15;546(7658):370-375.

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs. Bertero A, Pawlowski M, Ortmann D, Snijders K, Yiangou L, Cardoso de Brito M, Brown S, Bernard WG, Cooper JD, Giacomelli E, Gambardella L, Hannan NR, Iyer D, Sampaziotis F, Serrano F, Zonneveld MC, Sinha S, Kotter M, Vallier L. Development. 2016 Dec 1;143(23):4405-4418.

Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells. Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N, Koike-Yusa H, Kumasaka N, Vallier L, Yusa K, Bradley A. PLoS Genet. 2016 Apr 7;12(4):e1005932.

Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by Cyclin D. Pauklin S, Madrigal P, Bertero A, Vallier L. Genes Dev. 2016 Feb 15;30(4):421-33.

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells. Butcher LM, Ito M, Brimpari M, Morris TJ, Soares FA, Ährlund-Richter L, Carey N, Vallier L, Ferguson-Smith AC, Beck S. Nat Commun. 2016 Jan 29;7:10458.

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Sampaziotis F, Cardoso de Brito M, Madrigal P, Bertero A, Saeb-Parsy K, Soares FA, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WT, Davies S, Baker A, Kaser A, Alexander GJ, Hannan NR, Vallier L. Nat Biotechnol. 2015 Aug;33(8):845-52.

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors. Cebola I, Rodríguez-Seguí SA, Cho CH, Bessa J, Rovira M, Luengo M, Chhatriwala M, Berry A, Ponsa-Cobas J, Maestro MA, Jennings RE, Pasquali L, Morán I, Castro N, Hanley NA, Gomez-Skarmeta JL, Vallier L, Ferrer J. Nat Cell Biol. 2015 May;17(5):615-26.

Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark. Bertero A, Madrigal P, Galli A, Hubner NC, Moreno I, Burks D, Brown S, Pedersen RA, Gaffney D, Mendjan S, Pauklin S, Vallier L. Genes Dev. 2015 Apr 1;29(7):702-17.

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