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B5: Comparative functional profiling of human stem cells

Project leader: Prof. Dr.  F. Buchholz 

Adult stem cells need to manage two opposing programs: regeneration of all somatic cell types by differentiation and, at the same time, permanent self-renewal to maintain a constant stem cell pool. Both programs are controlled by an interactive network of transcription factors and epigenetic regulators to ensure a healthy balance in this process. In the mouse we have uncovered such an interaction trough a genome-scale shRNA screen in primary hematopoietic stem/progenitor cells, where the transcription factor Runx1 and the epigenetic regulator Pcgf1 were found to cooperate to form differentiated hematopoietic cells. The evolutionary conservation for this cooperativity and its potential implication for human leukemia development will be investigated.

Furthermore, the technological expertise in genome-wide RNAi screening in primary cells will be translated to human. Different human stem cells, isolated from a single individual, will be functionally profiled. By comparing the results for each of the cell types we should be able to nominate common and specific genes that are required for growth and self-renewal. In addition, we should also be able to nominate genes that result in enhanced proliferation of common and specific stem cell types upon knockdown. Our work should form the basis for a comparative, systems-oriented understanding of omnipotent and pluripotent human stem cells.


« January 2020 »

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