PhD Projects on offer
Trophoblast differentiation in vitro and in vivo
Supervisors: Ashley Moffett and Kathy K Niakan
Human embryonic stem cells (hESCs) and mouse epiblast-derived stem cells (EpiSCs) both have the property of pluripotency and can even differentiate into extra-embryonic trophoblast when cultured for a limited period under conditions containing BMP4 signalling activity. In vivo, trophoblast will eventually differentiate into two main lineages, villous and extravillous that are characterized by distinctive gene expression patterns. In particular, cell surface HLA class I molecules can be used to define these two lineages as villous trophoblast are HLA null whilst extravillous trophoblast cells express a unique array of HLA-G, HLA-C and HLA-E molecules.
The aim of this project is to investigate trophoblast differentiation in vivo and in vitro with a particular focus on how the HLA expression pattern is acquired. hESCs, EpiSCs and primary trophoblast cells from early pregnancy will be used as the experimental material. The project will be shared between two laboratories with complementary expertise, Dr. Niakan having expertise in ESC differentiation and Prof Moffett having expertise in the expression and function of trophoblast HLA molecules.
Refs
Moffett, A and Loke, C (2006) Immunology of
placentation in eutherian mammals. Nature Reviews Immunol 6, 584-594. Apps et al
Trophoblast cell lines. Immunology in press
Brons, IG, Smithers LE, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA and Vallier L. (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448: 191-195.
Niakan K.K., Ji, H., Vokes, S., Rodolfa, K.T., Sherwood, R.I., Dimos, J., Chen, A.E., Maehr, R., Melton, D.A., McMahon, A.P., and Eggan, K. (2010) Sox17 promotes differentiation in mouse embryonic stem cell by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes and Dev, accepted.
