Hematopoietic Stem and Progenitor Cells Establish Dynamic Podosome-Like Structures to Interact with Fibronectin

To keep their stem cell properties, hematopoietic stem and progenitor cells (HSPCs) need to interact with their stem cell niche in the bone marrow. Yet, the way in which HSPCs anchor to this specific microenvironment composed of niche cells and extracellular matrix (ECM) is not well understood. Here, the adhesion structures established by HSPCs upon contact with the ECM component fibronectin are investigated with regard to their appearance, maturity state, and composition. HSPCs adhere in a dynamic manner and display varying morphologies, with most cells displaying a round shape and the establishment of many podosome-like structures (PLS). The PLS consist of F-actin puncta, co-localized with phosphorylated PYK2, vinculin, and paxillin. These proteins assemble towards the periphery of the structure, and this pattern is more pronounced in cells with a round shape and higher PLS numbers. We also find strong indications that cells with a round shape or displaying higher levels of PLS are less differentiated and less likely to be of myeloid lineage. The study highlights the dynamic adhesion behavior of HSPCs and points to PLS as structures of interest in the interaction between these cells and their niche. Podosome-like structures are found in the majority of hematopoietic stem and progenitor cells. These structures are more maturely established in round cells, and cells establishing the structures in higher quantities are more naïve.