Lasarev, M. R. | bioRxiv Science

bioRxiv2025

Vcam1 in endothelial and stromal cells regulates hematopoietic stem cell contact with the niche

Hematopoietic stem and progenitor cells (HSPCs) are essential for differentiation into all blood cell types. In mammals, the interaction between HSPCs and the fetal liver niche during development is critical for stem cell maturation. Integrin alpha 4 (Itga4) on HSPCs and vascular cell adhesion molecule (Vcam1) on niche cells are critical for HSPC colonization of the fetal liver (FL). Itga4 and Vcam1 also function in the zebrafish equivalent of the FL, the caudal hematopoietic tissue (CHT), however, the specific niche cells that express Vcam1 remain unclear. Using multiple approaches, including fluorescent in situ hybridization, we found Vcam1 is expressed in endothelial cells (ECs) and mesenchymal stromal cells (MSCs), but not macrophages. Time-lapse live imaging of itga4 mutants showed the Itga4-Vcam1 axis is required for HSPC retention in the CHT niche, but not homing or lodgment. Our results show that Itga4 on HSPCs and Vcam1 on ECs and MSCs are involved in retention in the CHT niche. SummaryBlood stem cell interaction with the niche microenvironment during development is critical for establishing a robust stem cell pool into adulthood. This study determines the niche cell types that present Vcam1 in the embryo and allow interaction with blood stem cells.

developmental biology↗

bioRxiv2024

Real time imaging reveals a role for macrophage protrusive motility in melanoma invasion

Macrophages are primary cells of the innate immune system that mediate tumor progression. However, the motile behavior of macrophages and interactions with tumor cells are not well understood. Here, we exploit the optical transparency of larval zebrafish and perform real time imaging of macrophage-melanoma interactions. We found that macrophages are highly motile in the tumor microenvironment. Macrophages extend dynamic projections between tumor cells that precedes invasive melanoma migration. Modulating macrophage motility with a dominant inhibitory mutation in Rac2 inhibits recruitment to the tumor and impairs tumor invasion. However, a hyperactivating mutation in Rac2 does not affect macrophage recruitment but limits macrophage projections into the melanoma mass and reduces invasive melanoma cell migration. Taken together, these findings reveal a role for Rac2-mediated macrophage protrusive motility in melanoma invasion.

cell biology↗