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B3: Characterization and functional relevance of nanotubular highway-like structures that physically link hematopoietic stem and progenitor cells over long distances

Project leader: Dr. D. Corbeil

Cell-to-cell communication is a prerequisite for the development and maintenance of multicellular organisms and various mechanisms for the exchange of information between cells have been documented. One of them relies on the formation of thin plasma membrane protrusions (referred to as nanotubular highways (NTHs)). They bridge cells over long distances. Numerous cargo molecules and/or electric signal could be transported along NTHs in various biological processes. Although NTHs are the subject of intense research, little is known about them in stem cells. In order to characterize cell biological phenomena occurring in the bone marrow niche we established a co-culture system consisting of human CD34+ hematopoietic stem and progenitor cells (HSPCs) growing on bone marrow-derived mesenchymal stromal cells. We observed that adjacent HSPCs develop thin plasma membrane processes similar to NTHs. Here, we propose to explore their relevance. We plan i) to document their composition; ii) to dissect the molecular mechanism underlying their formation; iii) to determine whether they play a direct role in intercellular communication of HSPCs; iv) to determine the influence of HSPC proliferation and differentiation on their biogenesis, v) to document them in vivo, and vi) to characterize them in hematopoietic cancer cells. Collectively, such information should bring new insights into the cell biology of HSPCs and novel facets of the bone marrow microenvironment.

« September 2019 »

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