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Konstantinos Anastassiadis
Mechanisms that control the totipotency and differentiation of mouse ES cells
Previous and current research
The research interest in my lab is to unravel the molecular pathways that regulate self-renewal and lineage commitment of stem cells and the molecular mechanisms that are involved in cellular reprogramming. We work with mouse and human embryonic stem cells (mES, hES), neural stem cells (NSCs), mesenchymal stromal cells (MSCs) and induced pluripotent stem cells (iPS). My lab is also focusing on the development of genetic engineering tools that can be used to address the above questions. A short overview of the projects in my lab is presented below:
1. Development of new genetic engineering tools. We generated deleter and reporter mice for a new site-specific recombinase, named Dre and mice using C57Bl/6 ES cells with Flpo, a codon optimized version of the Flp-recombinase. Further we established methods for BAC transgenesis and gene targeting in human embryonic stem cells.
2. Conditional immortalization as a system for expansion of
rare cell types. The system is based on tetracycline regulated expression of
SV40 Large T Antigen and enables the isolation of adult cell types for
conditional expansion. We performed cellular cloning of mesenchymal stomal
cells isolated from tet-regulated Large T Antigen mice and identified
polulations with distinct differentiation properties.
3. Identification of the molecular mechanisms involved in somatic cell reprogramming. The aim is to elucidate the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) in the efficiency of reprogramming. An assay for induced reprogramming from mouse NS cells using transposase-mediated delivery of the reprogramming factors has been established. For testing the effect of the HMTs or HDMs we use tetracycline regulated overexpression or conditional mutagenesis.
Future prospects and goals
Correction of patient specific induced pluripotent stem cells by gene targeting
Dissect the role of histone demethylases in cellular reprogramming
Conditional immortalization for analyzing the lineage commitment of conditioanlly immortalized mesenchymal stromal cells
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Selected publications
Andreu-Vieyra, C. V., Chen, R., Agno, J. E., Glaser, S., Anastassiadis, K., Stewart, A. F. and Matzuk, M. M. (2010): "MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing." PLoS Biol 8.
Kranz, A., Fu, J., Duerschke, K., Weidlich, S., Naumann, R., Stewart, A. F. and Anastassiadis, K. (2010): "An improved Flp deleter mouse in C57Bl/6 based on Flpo recombinase." Genesis.
Anastassiadis, K., Rostovskaya, M., Lubitz, S., Weidlich, S. and Stewart, A. F. (2010): "Precise conditional immortalization of mouse cells using tetracycline-regulated SV40 large T-antigen." Genesis
Anastassiadis, K., Fu, J., Patsch, C., Hu, S., Weidlich, S., Duerschke, K., Buchholz, F., Edenhofer, F. and Stewart, A. F. (2009): "Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice." Dis Model Mech 2: 508-15.
Cambridge, S. B., Geissler, D., Calegari, F., Anastassiadis, K., Hasan, M. T., Stewart, A. F., Huttner, W. B., Hagen, V. and Bonhoeffer, T. (2009): "Doxycycline-dependent photoactivated gene expression in eukaryotic systems." Nat Methods 6: 527-31.
Glaser, S., Lubitz, S., Loveland, K. L., Ohbo, K., Robb, L., Schwenk, F., Seibler, J., Roellig, D., Kranz, A., Anastassiadis, K. and Stewart, A. F. (2009): "The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis." Epigenetics Chromatin 2: 5.
Lubitz, S., Glaser, S., Schaft, J., Stewart, A. F. and Anastassiadis, K. (2007): "Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2." Mol Biol Cell 18: 2356-66.