Cell & Regenerative Biology Department
The hematopoietic stem cell niche
4507 WIMR II
1111 Highland Ave.
Madison, WI 53705
Cell Adhesion & Cytoskeleton; Developmental Biology & Regenerative Medicine; Immunology
We use multiple approaches and model organisms to understand the fundamental biology that regulates hematopoietic stem cells (HSCs) in their niche. Harnessing the strength of each model, we are building a dynamic view of stem cell behavior in relation to multiple niche cell types. HSCs are concurrently regulated by many different cell types, including endothelial and mesenchymal stromal cells, as well as other hematopoietic cells. The hematopoietic system is very highly conserved so data from mouse and zebrafish often translates to humans.
We use zebrafish because they are a well-characterized functional genetic model with endogenous labels that allow direct live imaging of the endogenous niche. This allows us to test novel hypotheses that could not be performed in any other model system. The high efficiency of CRISPR/Cas9 gene editing in zebrafish now allows the rapid generation of mutant models. Together with transgenic fluorescent reporters of hematopoietic stem cells and many niche cell types, we can track live cellular interactions in wild-type and mutant genetic backgrounds. We are using correlative light and electron microscopy (CLEM) to look at the ultrastructure of endogenous HSCs in their niche.
We use mouse as an established HSC transplant model with an extensive panel of markers that can be used to dissect in fine detail changes within the hematopoietic system. We are currently focused on neurotransmitters that are found in the bone marrow niche, and neuroreceptors that are expressed on HSCs themselves. We are finding fascinating novel regulatory mechanisms that have the potential to improve clinical HSC transplantations.