Embryonic stem (ES) cells are derived from the inner cell mass of the embryo at the blastocyst stage. They can be maintained in culture and instructed to differentiate towards virtually any cell type of the body, thereby providing a powerful tool to study developmental processes in vitro. In addition, they are a promising source for future cell therapy applications, which aim at replacing cells lost in pathological conditions such as Parkinson’s disease, myocardial infarction, diabetes, and other major human diseases.
We are interested in using ES cells to study gene expression fluctuations and the molecular basis of cell fate choices during early developmental events. To address these questions, we use a broad range of techniques with a strong focus on single-cell live imaging approaches.
We are particularly interested in the following questions:
1) How does gene expression fluctuate in ES cells, and to what extent do these fluctuations influence cell fate decisions ?
2) What are the gene regulatory networks driving differentiation towards different fates ?
3) What is the role of retention of transcription factors on mitotic chromosomes in cell fate decisions ?
Alber AB*, Paquet ER*, Biserni M, Naef F, Suter DM. Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates
Molecular Cell 2018 Aug 23. [Epub ahead of print]
Deluz C*, Friman ET*, Strebinger D*, Benke A, Raccaud M, Callegari A, Leleu M, Manley S, Suter DM. A role for mitotic bookmarking of SOX2 in pluripotency and differentiation.
Genes & Development 2016 Dec 5. [Epub ahead of print]
Molina N*, Suter DM*†, Zoller B, Gotic I, Naef F†. Stimulus-induced modulation of transcriptional bursting in a single mammalian gene. *Equal contribution; †Corresponding authors
PNAS, 2013 Dec 17;110(51):20563-8
Gebhardt JCM* Suter DM*, Roy R, Zhao ZW, Chapman A, Basu S, Maniatis T, Xie XS. Probing Transcription Factor DNA Binding at the Single Molecule Level in Live Mammalian Cells. *Equal contribution. Nature Methods, 2013 Aug;10(8):692
Stratmann M*, Suter DM*, Molina N, Naef F, Schibler U. Circadian Dbp Transcription Relies on Highly Dynamic BMAL1-CLOCK Interaction with E Boxes and Requires the Proteasome. *Equal contribution.
Molecular Cell. 2012 Oct 26;48(2):277-87
Suter DM, Molina N, Naef F, Schibler U. Origins and consequences of transcriptional discontinuity.
Current Opinion in Cell Biology. 2011 Dec;23(6):657-62. Epub 2011 Sep 29.
Suter DM*, Molina N*, Gatfield D, Schneider K, Schibler U, Naef F. Mammalian genes are transcribed with widely different bursting kinetics. *Equal contribution
Science. 2011 Apr 22;332(6028):472-4
Suter DM, Tirefort D, Julien S, Krause KH. A Sox1 to Pax6 switch drives neuroectoderm to radial glia progression during differentiation of mouse embryonic stem cells.
Stem Cells. 2009 Jan;27(1):49-58.
Suter DM, Cartier L, Bettiol E, Tirefort D, Jaconi ME, Dubois-Dauphin M, Krause KH. Rapid generation of stable transgenic embryonic stem cell lines using modular lentivectors.
Stem Cells. 2006 Mar;24(3):615-23.