Signaling networks during hematopoietic ontogeny
Like all cells, HSCs are controlled by a complex cascade of signaling pathways that are either synergistic or antagonistic and ultimately determine cell decisions. Inflammatory signaling pathways like TLR, TNF, IFN were mostly associated with immune cells, but recently, it was shown that they can directly stimulate hematopoietic stem cells both under steady-state and stress conditions.
Furthermore, inflammatory signaling was proven to be indispensable for HSCs emergence. We focus on understanding how inflammatory signaling affects HSC formation during hematopoietic development.
Furthermore, our studies target on uncovering how inflammatory signaling can synergize with developmental pathways like Wnt, Notch and BMP to orchestrate HSCs development. We use zebrafish and mice to study HSC emergence and the epistatic interactions of different signaling pathways. We employ CRISPR-CAS9 technology, genetic and chemical screens, imaging and other methods in mice and zebrafish to unravel how HSCs are formed during EHT.
Ultimately we follow the knowledge that we gain from the embryonic system in adult hematopoiesis. We examine how different inflammatory sensors are essential for the maintenance of the hematopoietic system in adult zebrafish and mice (Figure 1).