ICAM-1 deficiency in the bone marrow niche impairs quiescence and repopulation of hematopoietic stem cells

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 favors 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 HSCs 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. Overall design: WT donor LSK (Ly5.1+) were sorted after transplanted into WT (n=3) or ICAM-1-/- (n=3) recipients (Ly5.2+) for 8 weeks, we analysis the transcriptional profile of LSK hematopoietic stem cells after transplantation by High-throughput RNA-sequencing.

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Liu YF, Zhang SY, Chen YY, Shi K, Zou B, Liu J, Yang Q, Jiang H, Wei L, Li CZ, Zhao M, Gabrilovich DI, Zhang H, Zhou J