Osteopontin is an important regulative component of the fetal bone marrow hematopoietic stem cell niche

Abstract

Osteopontin (OPN) is an important component in both bone and blood regulation, functioning as a bridge between the two. Previously, thrombin-cleaved osteopontin (trOPN), the dominant form of OPN in adult bone marrow (BM), was demonstrated to be a critical negative regulator of adult hematopoietic stem cells (HSC) via interactions with α4β1 and α9β1 integrins. We now demonstrate OPN is also required for fetal hematopoiesis in maintaining the HSC and progenitor pool in fetal BM. Specifically, we showed that trOPN is highly expressed in fetal BM and its receptors, α4β1 and α9β1 integrins, are both highly expressed and endogenously activated on fetal BM HSC and progenitors. Notably, the endogeno..