Stem cells and phenotype specification in neural lineage development - Regulation of growth and differentiation in human stem cell systems

• Applicant: Professor Dr. Jan Pruszak
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 188562905

The experiments outlined in this proposal will significantly enhance present knowledge of lineage specification and cell-cell interactions in human neural development. The development of the neural lineage (neuropoiesis) encompasses a number of highly fine-tuned stages and transitions. Major research efforts are aimed at the differentiation of pluripotent stem cells (PSCs) into biomedically relevant phenotypes. However, overall, our understanding of signaling pathways and regulatory networks underlying neural morphogenesis and phenotype specification has remained very limited. Current approaches of directed differentiation of PSCs result in inappropriate phenotypes and heterogenous, poorly controlled cultures, indicating that current in vitro protocols neglect the aspect of cell-cell interactions, and their relevance for appropriate patterning, positional specification and morphogenesis. To elucidate the nature of intercellular communication of such self-organized developmental systems, there is a need for investigating neural surface molecules and secreted factors as well as their respective interplay in the specification of neural phenotypes. We hypothesize that a mechanistic understanding of the communication between hPSC-derived neural cells via their respective differential cell surface signature in combination with secreted factors/diffusible morphogens will enhance the differentiation of physiological cell types from human embryonic and induced pluripotent stem cells, which will enable the formulation and testing of novel hypotheses in the fields of neuroembryology and optimized generation of neural cells for biomedical applications including cell therapy.

• DFG Programme: Emmy Noether Independent Junior Research Groups