Laboratory of Hematopoietic Stem Cell Engineering, International Research Center for Medical Sciences, Kumamoto University, Chuo-Ku, Kumamoto, Japan; Laboratory of Stem Cell Stress, International Research Center for Medical Sciences, Kumamoto University, Chuo Ward, Kumamoto, Japan.
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Exp Hematol. 2024 Oct;138:104281. doi: 10.1016/j.exphem.2024.104281. Epub 2024 Jul 14.
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.
在应激造血过程中，先前的研究表明造血干细胞（HSCs）从骨髓（BM）迁移到骨髓外部位，如脾脏。然而，直接证明 HSC 从 BM 迁移到脾脏的证据很少。在这里，我们通过氟尿嘧啶（5-FU）诱导骨髓清除，并通过光转化荧光染料显示造血再生过程中 HSC 从 BM 直接迁移到脾脏的直接证据。此外，在稳态下，HSCs 优先迁移到 BM 而不是脾脏，但在造血再生期间，HSCs 同样或更多地优先选择脾脏作为迁移部位。此外，在早期阶段，HSCs 通过减弱的 HSC 保留从 BM 中移出。然而，晚期的 HSCs 获得了显著增强的自主运动能力，这与趋化性无关。总之，造血再生过程中，HSC 从 BM 动员到向脾脏迁移之前，其从被动到主动的迁移事件是动态变化的。
