Research
The processes of embryo implantation and the initiation of placental development are pivotal in the establishment and maintenance of a healthy pregnancy. In humans, around 30% of conceptions are lost in the early post-implantation period and poor placentation often underlies later complications of pregnancy such as preeclampsia and intrauterine growth restriction. There is still much to learn about the molecular mechanisms underpinning these very early developmental processes.
Post-transcriptional regulatory mechanisms are an understudied facet of mammalian development, and I am particularly interested in the pathways controlling mRNA stability and decay at key cell state transitions during the early postimplantation period. In the lab I use embryonic and trophoblast stem cells in culture, as well as in vivo models, to understand how RNA decay factors contribute to normal development with a focus on the placental trophoblast lineages which are foundational for reproductive success.
Publications
Senner C.E., Dong Z., Prater M., Branco M.R. and Watson E.D. (2023). One-carbon metabolism is required for epigenetic stability in the mouse placenta. Front Cell Dev Biol. 11:1209928.(co-corresponding)
Senner C.E., Chrysanthou S., Burge S., Lin H-Y., Branco M. and Hemberger M.† (2020). TET1 and 5-hydroxymethylation preserve the stem cell state of mouse trophoblast. Stem Cell Reports. 15, 1301-1316. (co-corresponding)
Schoenfelder S., Mifsud B., Senner C.E., Todd C.D., Chrysanthou S., Darbo E., Hemberger M., and Branco M.R. (2018). Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages. Nat Commun. 9, 4189.
Chrysanthou S., Senner C.E., Woods L., Fineberg E., Okkenhaug H., Burge S., Perez-Garcia V. and Hemberger M. (2018). A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells. Stem Cell Reports. 10, 1355-1368.
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.
Kubaczka, C., Senner, C., 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 30, 232-242.
Senner, C.E., Krueger, F., Oxley, D., Andrews, S., and Hemberger, M. (2012). DNA methylation profiles define stem cell identity and reveal a tight embryonic-extraembryonic lineage boundary. Stem Cells 30, 2732-2745.
Nesterova, T.B.*, Senner, C.E.*, Schneider, J., Alcayna-Stevens, T., Tattermusch, A., Hemberger, M., and Brockdorff N. (2011). Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells. Epigenetics Chromatin 4, 17. *equal contribution
Ohhata, T., Senner, C.E., Hemberger, M., and Wutz, A. (2011). Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice. Genes Dev. 25, 1702-1715.
Senner, C.E. (2011). The role of DNA methylation in mammalian development. Reprod. Biomed. Online 22, 529-535.
Senner, C.E., Nesterova, T.B., Norton, S., Dewchand, H., Godwin, J., Mak, W., and Brockdorff N. (2011). Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. Development 138, 1541-1550.
Senner, C.E., and Hemberger, M. (2010). Regulation of early trophoblast differentiation - lessons from the mouse. Placenta 31, 944-950.
Senner, C.E., and Brockdorff, N. (2009) Xist gene regulation at the onset of X inactivation. Curr. Opin. Genet. Dev. 19, 122-126.
