Cells can only arise from progenitor cells. This fundamental principle of biology also applies to differentiation processes. The von Haeseler group at CIBIV is interested in investigating to what extent phylogenetic approaches can contribute to a better understanding of molecular mechanisms that regulate neural progenitors and stem cells in space and time.

For this purpose, we will reproduce the differentiation process in a genealogical pedigree (phylogenetic tree) with the help of single cell sequencing technologies. We will characterize the physiological state of single cells from different stages of differentiation given that since single cells are most similar to their precursor cells.

Current methods categorize the expression patterns of single cells along deterministic or probabilistic trajectories to show the differentiation pattern of all cells. However, these methods can only represent the true relationships of the differentiating cells to a limited extent. We are hypothesizing that phylogenetic methods are more powerful, because they delineate the true genealogical relationship among cells allowing us to traceback the most likely pre-cursor of a specific differentiated cell and, for instance, its expression pattern. This approach is fundamentally different from existing approaches that describe how a cloud of undifferentiated cells changes continuously.

Our analysis is based on the biological principle of the genealogical relationship of cells and should therefore better reflect true development. To test the biological relevance of our findings, we will use the entire statistical repertoire of phylogenetic inference to check for statistical significance in our models. Such statistical methods do not currently exist for the analysis of single-cell trajectories. We will provide a completely new method to study differentiation processes from single cell data and work together with the consortium to offer a common bioinformatics platform.

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