Itga8+ MSCs in the endosteal niche contribute to the maintenance of hematopoietic stem cell self-renewal capacity.

The bone marrow (BM) niche is a specialized microenvironment critical for the maintenance and regulation of hematopoietic stem cells (HSCs). Different niches in the BM support HSCs, and among them we analyzed the endosteal niche. The endosteal niche is formed by Alcam+ Sca-1- osteoblasts, Alcam- Sca-1+ mesenchymal stem cells (MSCs), and Alcam- Sca-1- cells. Using single-cell gene expression analysis, we identified a unique subpopulation within the Alcam+ Sca-1- bone-lining cells (BLCs) that lacked osteoblast markers. This subpopulation was found to be a novel MSC with specific expression of the 8-integrin (Itga8). We compared gene expression between Itga8+ Alcam+ Sca-1- MSCs (Itga8+ MSCs), Itga8- Alcam+ Sca-1- BLCs, Alcam- Sca-1+ MSCs, and CD51+ CD140a+ MSCs to investigate the characteristics of Itga8+ MSCs. Itga8+ MSCs showed a distinct gene expression profile compared with the others, demonstrating that Itga8+ MSCs are different from previously reported BLCs and MSCs. Furthermore, Itga8+ MSCs were found to secrete extracellular matrix (ECM) that regulates HSCs, and therefore, Itga8+ MSCs are important MSCs that provide the ECM required to maintain HSCs within the endosteal niche.