Abstract:
Under stress hematopoiesis, previous studies have suggested the migration of hematopoietic stem cells (HSCs) from bone marrow (BM) to extramedullary sites such as the spleen. However, there is little direct evidence of HSC migration from the BM to the spleen. Here, we induced myeloablation via 5-fluorouracil (5-FU) and showed direct evidence of HSC migration from BM to spleen during hematopoietic regeneration via a photoconvertible fluorophore. Moreover, during steady state, HSCs preferentially migrated to BM rather than spleen, but during hematopoietic regeneration, HSCs preferred spleen as a migration site equivalently or greater. Furthermore, in the early phase, HSCs egressed from BM through the attenuated HSC retention. However, HSCs in the late phase gained significantly enhanced cell-autonomous motility, which was independent of chemotaxis. Collectively, HSC mobilization from BM, before the migration to the spleen, was dynamically changed from passive to active events during hematopoietic regeneration.
摘要:
在应激造血下,以前的研究表明造血干细胞(HSC)从骨髓(BM)迁移到髓外部位,如脾脏。然而,几乎没有直接证据表明HSC从BM迁移到脾脏。这里,我们通过5-氟尿嘧啶(5-FU)诱导骨髓消融,并显示了造血再生过程中HSC通过光转化荧光团从BM迁移到脾脏的直接证据。此外,在稳态期间,HSC优先迁移到BM而不是脾脏,但是在造血再生过程中,HSC更喜欢脾脏作为同等或更大的迁移位点。此外,在早期阶段,通过减弱的HSC保留从BM中排出的HSC。然而,晚期HSC获得了显著增强的细胞自主运动,这与趋化性无关。总的来说,在造血再生过程中,在迁移到脾脏之前,从BM动员的HSC从被动事件动态变化为主动事件。