Professor of Regenerative Medicine
Departments and Institutes
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.
ES (embryonic stem cells) ; regenerative medicine ; iPSC ; iPS (induced pluripotent stem cells) ; stem cells
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.