Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells.

摘要: Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, mechanisms underpinning this remain to be fully defined. The studies described herein examine in hematopoiesis of Osteopontin (Opn), multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate previously unrecognized critical for Opn regulation physical location proliferation HSCs. Within marrow, expression is restricted endosteal bone surface contributes HSC transmarrow migration toward region, as demonstrated markedly aberrant distribution HSCs Opn–/– mice after transplantation. Primitive cells specific adhesion vitro via β1 integrin. Furthermore, exogenous potently suppresses primitive HPCs vitro, physiologic relevance which enhanced cycling mice. These therefore provide strong evidence an important component niche participates physiologic-negative regulator proliferation.