Novel regulators of trophoblast stem cell potential
Trophoblast Stem Cells (TSCs) are a self-renewing stem cell population derived from the early embryo that can give rise to all cell types of the placenta. They are an invaluable research tool for our understanding of developmental defects and pregnancy complications. Yet TSCs are a heterogeneous cell population, and the critical factors required for maintaining the self-renewal potential of TSCs are still fairly poorly explored.
This project will explore the heterogeneity of TSC populations by single cell-sequencing approaches to determine the naive and primed state of developmental potency of TSCs. The student will also generate reporter alleles to trace and sort naïve TSCs and investigate the molecular and epigenetic basis that underpins this state by ChIP-seq analysis for histone modifications, transcription factor occupancy and DNA methylation states.
Key candidates for maintaining TSC potential will be knocked out by CRISPR-Cas9 mediated technology, and arising null colonies screened for their self-renewal ability and the rate and trajectory of differentiation. The student will employ a large range of state-of-the-art techniques during this project, including single cell sequencing methods, in-depth bioinformatic analysis, stem cell culture, CRISPR gene knockout strategies, ChIP-seq and methylation mapping, flow cytometry and, high-level imaging techniques. The insights gained will be instrumental to advance research into the regulation of stem cell plasticity and developmental potency.
For further details please contact me at Lab Twitter Account: @HembergerLab
Lab Website: http://www.babraham.ac.uk/our-research/epigenetics/myriam-hemberger
- Murray A., Sienerth A. and Hemberger M. (2016). Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation. Scientific Reports, 6: 25112.
- Lee C.E.Q., Gardner L., Turco M., Zhao N., Murray M.J., Coleman N., Rossant J., Hemberger M. and Moffett A. (2016). What is trophoblast? A combination of criteria define human first trimester trophoblast. Stem Cell Reports, 6 :257-272.
- Branco M.R., King M., Perez-Garcia V., Bogutz A.B., Caley M., Fineberg E., Lefebvre L., Cook S.J., Dean W., Hemberger M.* and Reik W.* (2016). Maternal DNA methylation regulates early trophoblast development. Developmental Cell 36: 152–163. *Co-senior authors.
- Latos P.A., Sienerth A.R., Murray A., Senner C.E., Muto M., Ikawa M., Oxley D., Burge S., Cox B. and Hemberger M. (2015). Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks. Genes & Development, 29: 2435-2448.
- Kubaczka C., Senner C.E., Cierlitza M., Araúzo-Bravo M.J., Kuckenberg P., Peitz M., Hemberger M. and Schorle H. (2015). Direct induction of trophoblast stem cells from murine fibroblasts. Cell Stem Cell, 17: 557-568.
- Latos P.A., Goncalves A., Oxley D., Mohammed H., Turro E. and Hemberger M. (2015). Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells. Nat. Commun., 6: 7776.
- Cambuli F., Murray A., Dean, W., Dudzinska D., Krueger F., Andrews S., Senner C.E., Cook S. J. and Hemberger M. (2014). Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast. Nat. Commun., 5: 5538.
- Roper S.J., Chrysanthou S., Senner C.E., Sienerth A., Gnan S., Murray A., Masutani M., Latos P. and Hemberger M. (2014). ADP-ribosyltransferases Parp1 and Parp7 safeguard pluripotency of ES cells. Nucleic Acids Research, 42: 8914-8927.
- Kubaczka C., Senner C.E., Araúzo-Bravo M.J., Sharma N., Kuckenberg P., Becker A., Zimmer A., Brüstle O., Peitz M., Hemberger M. and Schorle H. (2014). Derivation and maintenance of murine trophoblast stem cells under defined conditions. Stem Cell Reports, 2: 232-242.
- Latos P. and Hemberger M. (2014). The transcriptional and signalling networks of trophoblast stem cells. Placenta/Trophoblast Research, 35: S81-85.