Maintaining and Reprogramming Cell Fates

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Maintaining and Reprogramming Cell Fates

How do cells remember their identity? How can we change cell fates by nuclear reprogramming?

Differentiated cells in our body rarely, if ever, change their cell type: They have a cellular memory of their identity which prevents unwanted cell fate changes in healthy organisms which may be circumvented in disease. However, vertebrate eggs have the remarkable ability to reprogram cell fates when the nucleus of a somatic cell is transferred to an enucleated egg. The so generated nuclear transfer embryo can erase the cellular memory of the previous cell identity, allowing the establishment of totipotency, and can so give rise to all cell types of the body:

 

This has a fundamental impact on regenerative medicine, as progress in understanding the molecular mechanisms of nuclear reprogramming of cell fates could allow the generation of any cell type on demand, as needed for cell replacement therapies. Despite this enormous potential, the molecular mechanisms that enable, drive, or resist the conversion of cell fates remain elusive:

+ What are the epigenetic mechanisms that stabilise differentiated cell fates and inhibit reprogramming of cell fates in nuclear transfer embryos?

+ What are the molecular processes during reprogramming to totipotency in vertebrate eggs?

+ How does cellular “ON-memory” inhibit the establishment of a new cell fate?

To study these questions, we make use of a classic system - somatic cell nuclear transfer to Xenopus eggs, and combine it with innovative multi-omics approaches, biochemical and cell biological assays as well as computational approaches including machine learning. The gained knowledge of the molecular mechanisms of nuclear reprogramming will then ultimately allow us to achieve a fast, efficient and complete switch in cell fate directly or within few cell cycles. The identification of the epigenetic signatures that inhibit nuclear reprogramming will help to improve current reprogramming strategies and will give crucial insights into the safeguarding mechanisms of cells that prevent unwanted changes in cell fate during development and ageing.

 

 

 

 

 

 

 

 

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