ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells

Abstract

Summary: The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1−/−) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favoring myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSC quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1−/− mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche. : In this article, Jie Zhou and colleagues show that ICAM-1 expression in bone marrow niche contributes to the quiescence and repopulation capacity of HSCs. ICAM-1 deficiency changes the expression profile of stroma-derived factors, thus causing failure of HSC retention in the bone marrow. Clinical data indicate that ICAM-1 might participate in the progression of myelocytic leukemia. Keywords: hematopoietic stem cells, homeostasis, intercellular adhesion molecule-1, bone marrow niche