Endosteal integrin-α8⁺ mesenchymal stem cells maintain haematopoietic stem cell function via extracellular matrix-mediated interactions

Abstract

Abstract The stem cell niche is a specialised microenvironment essential for maintaining haematopoietic stem cells (HSCs). Here we identify a distinct subset of mesenchymal stem cells (MSCs) expressing integrin α8 (Itga8⁺ MSCs) within the bone marrow (BM) endosteum. These cells exhibit distinct MSC properties and higher haematopoietic supportive activity than other MSC subsets. Depletion of Itga8⁺ MSCs decreased HSC numbers, reduced quiescence of endosteal HSCs and diminished BM repopulating capacity. Itga8⁺ MSCs support haematopoiesis through cell adhesion-related mechanisms. Single-cell RNA sequencing further identified Itga8⁺ MSCs as a distinct subpopulation within bone-lining cells. Moreover, we identified Mfap4 as a candidate factor expressed in Itga8⁺ MSCs, and Mfap4 supported the BM reconstitution capacity of HSCs. These results suggest that Itga8⁺ MSCs represent a distinct niche cell population for HSC maintenance. This work provides new insights into HSC regulation and strategies to optimise in vitro HSC maintenance and enhance in vivo engraftment.