Hematopoietic potential cells in skeletal muscle

Abstract

During mouse embryogenesis, the formation of primitive hematopoiesis begins in the yolk sac on embryonic day 7.5 (E7.5). Thereafter, definitive hematopoietic stem cell (HSC) activity is first detectable in the aorta-gonad-mesonephros (AGM) region on E10, followed by fetal liver and yolk sac. Subsequently, the fetal liver by E12 becomes the main tissue for definitive hematopoiesis. At a later time, HSC population in the fetal liver migrates to the bone marrow, which becomes the major site of hematopoiesis throughout normal adult life 1. It remained unclear whether hematopoietic stem/progenitor cells exist in non-hematopoietic tissues. In 1980s, Bartlett 2 first described that adult mouse brain contained significant amount of colony forming units (CFU-s). The average number of CFU-s obtained per 105 dissociated adult brain cells was significantly higher than other adult tissues such as lung, kidney, heart, thymus and blood. However, Hoogerbrugge et al. 3 could not obtain such high number of CFU-s in adult brain and concluded that the CFU-s observed by Bartlett in preparations of mouse brain did not originate from the brain tissue. Nevertheless, recent work revealed that hematopoietic stem/progenitor cells clearly exist in several tissues besides bone marrow 4, 5. For example, adult liver has been shown to contain HSCs that reconstitute whole hematopoiesis in lethally irradiated animals. HSCs and hematopoietic progenitor cells readily colonize the adult spleen. In addition, adult lung contains large numbers of alveolar macrophages derived from progenitors identified in fetal lung. Furthermore, T cell differentiation occurs in extra-thymic sites, such as intestine and liver.