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A quantitative analysis of single cell variation in transcription during the stabilisation of neural mesodermal cell states in vivo and in vitro (QUANT CELL STATE)
Start date: May 19, 2014, End date: May 18, 2016 PROJECT  FINISHED 

The ability to manipulate cellular processes such as differentiation represents one of the major challenges of modern biological research. Central to this is the ability to ensure that target cells respond to signals in a highly coordinated manner, such that all cells within a population respond in the desired way. During embryonic development, cells within a population or tissue interpret a multitude of external signals with remarkable reproducibility as they become specified. Therefore, it is of the upmost interest to understand how this coordinated response is achieved as cells undergo cell fate decisions in vivo and the degree to which this robustness is conserved as stem cells are induced to differentiate in vitro. We aim to quantify transcriptional dynamics at the single cell level as cells move from a stem cell transition state to stabilized neural and mesodermal cell states. This will be performed initially for tailbud stem cells in zebrafish in vivo and subsequently as mouse embryonic stem cells are induced to differentiate in vitro. We expect that this study will not only provide fundamental insights into the dynamics of transcriptional regulation as cells undergo cell state transitions, but also provide highly sensitive fingerprints with which to analyse the molecular mechanisms that control and coordinate cell specification. These studies will be performed in experimental systems that are highly amiable for molecular and genetic manipulations both in an in vivo and an in vitro context and hence lead to a broad and collaborative research programme aimed at understanding the mechanics of coordinated cell state stabilization.
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