THE SINUSOIDAL ENDOTHELIUM FUNCTIONS AS A HEMATOPOIETIC NICHE IN THE ZEBRAFISH KIDNEY

Hematopoietic stem cells (HSCs) are maintained in the specific microenvironment, termed the HSC niche. Some essential cellular components of HSC niches have been identified in the murine bone marrow, such as sinusoidal endothelial cells, perivascular cells, and mesenchymal stem cells. The zebrafish is an excellent model for the study of HSCs due to its many unique advantages, including valuable tools and experimental methods (e.g. transgenic/mutant animals, transplantation assays, cell culture assays, etc.). Moreover, the major hematopoietic organ in zebrafish is the kidney, so-called the “kidney marrow”, providing a parallel view of the HSC niche over evolution. Little is known, however, regarding which cell types plays a role in HSC niches in the kidney. This is due in part to the lack of robust methods to purify HSCs from the zebrafish kidney. Here, we show that zebrafish HSCs are highly enriched in the double-positive fraction of gata2a:GFP and runx1:mCherry (gata2a+ runx1+), and that gata2a+ runx1+ cells are closely associated with the sinusoidal endothelium in the adult kidney. An in vivo competitive repopulation assay showed that the frequency of HSCs was at least 550 times higher in gata2a+ runx1+ cells than total hematopoietic cells in the zebrafish kidney. Histological analyses revealed that gata2a+ runx1+ cells were mainly observed in the dorsal lateral area of the kidney where sinusoidal capillaries are abundantly observed. Loss of Jam1a, which is expressed in both sinusoidal endothelial cells and hematopoietic cells, led to a remarkable reduction in the sinusoidal area of the kidney and defect in supporting the hematopoietic repopulation. Our data thus suggest that the sinusoidal endothelium is an evolutionarily conserved component of HSC niches in vertebrates.