Differentiation of immune cells
As a model of multi-lineage differentiation we are studying cells of the hematopoietic system with a focus on lymphocytes. Years of intense research have revealed the major hematopoietic cell types as well as multipotent progenitor populations with the help of flow cytometry on the basis of a relatively small number of cell surface markers. The development of sensitive high-throughput single-cell sequencing has revolutionized the identification of cell types and differentiation trajectories, and recent studies are changing our model of hematopoietic differentiation.
We are studying differentiation of murine lymphoid cell populations in primary lymphoid organs, i.e. bone marrow and thymus, as well as differentiation of tissue-resident cells of the innate immune system. Our aim is to elucidate spatial heterogeneity, e.g. across tissues, and temporal heterogeneity of immune cell differentiation during life. In more detail, we are trying to identify regulatory mechanisms underpinning lineage choice and to understand the role of gene expression variability in this context. By means of single-cell RNA-seq analysis we are trying to create a high-resolution map of cell states and the differentiation trajectories connecting these states. To obtain temporal information, we couple snapshot single-cell transcriptome data to differentiation history by means of lineage tracing.
Utilizing spatial transcriptomics and single molecule fluorescence in situ hybridization we investigate the role of the microenvironment in differentiation decisions.
Our strategy implies the identification of novel cell type or state specific markers, enabling the purification of homogenous sub-populations for functional studies, e.g. by in vivo or in vitro differentiation assays.