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

Recent publications:

1.   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.
2.   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.
3.   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.
4.   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.
5.   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.
6.   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.
7.   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.
8.   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.
9.   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.
10.   Latos P.   and Hemberger M. (2014). The transcriptional and signalling networks of   trophoblast stem cells. Placenta/Trophoblast Research, 35:   S81-85.