Inference of Differentiation Decision Times from Blood Stem Cell Genealogies

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In blood stem cells, differentiation can be experimentally assessedvia the expression of an appropriate fluorescent marker protein.Between the cellular decision and the observed fluorescent signal, acertain delay is involved. In this project, we want to infer the exacttime of differentiation from the marker onsets in hematopoieticgenealogies. The synchrony of marker onsets between sister cells,cousin cells, etc. allows disentangling the two processes involved:differentiation decision and marker activation. We will first generategenealogies from a generative model where we consider differentmolecular mechanism for the two processes. In parallel, wepost-process and analyze mouse blood cell genealogies (from theSchroeder lab, Stem Cell Dynamics research unit, Helmholtz ZentrumMünchen). These trees are generated from single-cell tracking oftime-lapse microscopy data and marker onset is either annotated orquantitatively determined. Development and application of treeinference methods will allow us to specify the decision time in eachgenealogy. From this we will delineate molecular mechanisms of markeractivation, the role of lineage determining factors, and possiblespatial effects on cellular differentiation. The methods developed inthis project can be transferred to any cellular genealogies ofdifferentiating and heterogeneous cell populations and arbitrarydifferentiation evidence, like morphological change or apoptosis in aspecific condition.