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B1: Elucidation of molecular networks controlling lineage commitment of bone marrow mesenchymal stromal cells

Project leader: Dr. K. Anastassiadis

Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors for skeletal tissues with poorly defined identity. Using a conditional immortalization strategy we were able to expand murine MSCs and identified clones that showed distinct differentiation properties (monopotential, bipotential or tripotential). By RNA-seq analysis we found distinct transcriptional signatures for all clones with osteogenic or adipogenic potential. Multipotent clones combined those signatures and didn’t represent unique identity. By high throughput screening of cell surface antigens we identified differentially expressed markers for the osteogenic and adipogenic lineages. In the 3rd funding period we aim to elucidate the molecular network of lineage commitment regulators by tagging candidate factors from our RNA-seq data and identifying their target genes and protein interaction partners. Further, we will study in vivo localization and function of different types of BM stromal progenitors by lineage tracing of cells expressing selected genes from our transcriptome analysis. Our findings will contribute to a better understanding of the physiological role of BM MSCs in regulating haematopoiesis and bone regeneration, which is a prerequisite for successful medical applications.

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Funding program:

DFG