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Research topics within the RTG 2578

The Research Training Group (RTG) "Impact of genotoxins on the differentiation efficacy of murine and human stem and progenitor cells and functional competence of thereof derived differentiated progeny" combines expertise in toxicology and stem cell biology within the Heinrich Heine University in a multidisciplinary centre of research and education. The research program employs disinct murine and human in vitro stem cell models comprising all germ layers.

The RTG 2578 deals with two main aspects:

  1. The analysis of differentiation-dependent alterations of factors that determine the susceptibility of stem (SC) and progenitor cells (PC) to model relevant DNA damaging agents (genotoxins).
  2. Investigating the impact of prototypical genotoxins (both environmental mutagens and anticancer drugs) on the efficacy and accuracy of the differentiation process and the functionality of the differentiated progeny.

To this end, the RTG 2578 employs different in vitro model systems and model-relevant genotoxic substances. The research activities will lead to the identification of cell-type specific susceptibility factors that affect genetic stability, and as a consequence, the differentiation efficacy and accuracy of stem and progenitor cells. Moreover, the functionality of the SC/PC-derived differentiated progeny will be extensively characterized. In this regard, the RTG will allow an in-depth characterization of the complex stress responses of different types of SC/PC and the related differentiated progeny following insults by prototypical (environmental and endogenously formed) genotoxins inducing different types of primary DNA damage.

In this manner, the RTG will promote the advancement of "integrated toxicological test systems" (ITS) that realize the "3R-principle" regarding animal testings. Furthermore, it will implement translational aspects related to regenerative and degenerative processes, embryonic development and carcinogenesis.

Distinct human and murine in vitro cellular differentiation models that represent different germ layers are used within the RTG 2578 in order to analyse the response of individual stem- and progenitor cells to model-relevant genotoxic agents. The implementation of various test systems and well-defined genotoxins together with an extensive analysis of relevant end points will foster multidisciplinary knowledge acquisition in genetic and developmental toxicology. As a result of the networked scientific research, synergistic effects are anticipated that favour knowledge in both basic research and translational concepts in distinct areas.

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