Geographical and functional determination of the hematopoietic stem cell niche
The hematopoietic stem cell (HSC) niche is located in the bone marrow (BM) in the adult and is the origin for all blood cells. The precise geographical location of the niche has remained elusive as different studies have described HSCs in proximity to the bone and osteoblasts, the vasculature and endothelial cells but also stromal cell components such as CXCL12-abundant reticular cells, Nestin+ cells, sympathetic nerves and non-myelinating Schwann cells, Lepr+ cells as well as Prx1+ cells.
In a current publication in Nature Paul Frenette and colleagues including SFB 914-associated principal investigator Christoph Scheiermann show that quiescent HSCs are predominantly located to an area that encompasses many of these components by associating with bone marrow arterioles.
Detailed ‘map’ of the HSC niche
The authors used a novel combination of whole-mount imaging and multi-color phenotyping to differentiate between structures in the BM in three dimensions and thus ‘map’ the localization of HSCs in situ. They could show that arterioles exhibit a well-structured ring-like organization that surrounds the central vein and is most prevalent closer to the endosteum. Arterioles are enwrapped by sympathetic nerves and NG2+-pericytes that define a subtype of Nestinperi-cells, which can be differentiated from Nestinretic-cells that are located close to BM sinusoids.
Transverse-shaved whole-mount images of the mouse femoral bone marrow stained with antibodies directed against VE-cadherin and PECAM-1 (white, left image, or blue, right image) highlighting the whole vasculature and Sca-1 (red, right image), marking arterioles.(Image by C. Scheiermann)
While quiescent HSCs associate with NG2+Nestinperi-cells, proliferating HSCs are found in proximity to Nestinretic-cells as induced by pharmacological or genetic activation of the HSC cell cycle. These results thus define the HSC niche in unprecedented detail and indicate that arteriolar niches are indispensable for maintaining HSC quiescence.
Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS. (2013)
Arteriolar niches maintain haematopoietic stem cell quiescence.
Nature 2013 Oct 9 [Epub ahead of print]
Dr. Christoph Scheiermann
Walter-Brendel-Zentrum für Experimentelle Medizin
Tel.: +49 (0)89-2180-76537