Stem Cell Genealogies

Inference of Differentiation Decision Times from Blood Stem Cell Genealogies

In blood stem cells, differentiation can be experimentally assessed via the expression of an appropriate fluorescent marker protein. Between the cellular decision and the observed fluorescent signal, a certain delay is involved. In this project, we want to infer the exact time of differentiation from the marker onsets in hematopoietic genealogies. 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 generate genealogies from a generative model where we consider different molecular mechanism for the two processes. In parallel, we post-process and analyze mouse blood cell genealogies from the lab of Timm Schroeder (ETH Zurich, BSSE Basel). These trees are generated from single-cell tracking of time-lapse microscopy data and marker onset is either annotated or quantitatively determined. Development and application of tree inference methods will allow us to specify the decision time in each genealogy. >From this we will delineate molecular mechanisms of marker activation, the role of lineage determining factors, and possible spatial effects on cellular differentiation. The methods developed in this project can be transferred to any cellular genealogies of differentiating and heterogeneous cell populations and arbitrary differentiation evidence, like morphological change or apoptosis in a specific condition.

Link to DFG-website