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After migration into blood circulation, hematopoietic stem cells can stably self-renew and maintain bone marrow while being skewed toward myeloid lineage when submitted to serial transplantation.
bioRxiv - Cell Biology Pub Date : 2021-03-04 , DOI: 10.1101/2021.03.04.433880
Yasmine Even , Lin Yi , Chih-Kai Chang , Fabio M. Rossi

Hematopoietic stem cells (HSCs) mainly reside in bone marrow (BM) within niches providing an appropriate environment for their survival and self-renewal. Although, small numbers of HSCs can quit their residing environment to migrate into blood circulation and re-engraft elsewhere in BM. Mobilizing agents such as granulocyte colony stimulating factor (G-CSF) can amplify this process by inducing massive HSC mobilization into blood circulation. This method is widely used in clinics to treat hematological disorders. However, in physiological conditions, the properties of HSCs after migration (called migratory HSCs) remain incompletely characterized. In this study, we investigated the capacity of migratory HSCs to self-renew, reconstitute and maintain BM. We show that after migration, HSCs can stably self-renew and maintain BM in homeostasis. However, while stably repopulating BM of irradiated recipients, migratory HSCs show a defect in lymphoid lineage reconstitution when subjected to serial transplantations. Our findings provide interesting knowledge on HSC properties after migration, which may benefits therapeutic research on HSC-based therapies to treat hematological disorders.

中文翻译:

移入血液循环后,造血干细胞可以稳定地自我更新并维持骨髓,而在进行系列移植时会偏向骨髓谱系。

造血干细胞(HSC)主要位于壁ni内的骨髓(BM)中,为它们的生存和自我更新提供了适当的环境。虽然,少数HSC可以退出其居住环境,以迁移到血液循环中并重新植入BM的其他位置。诸如粒细胞集落刺激因子(G-CSF)之类的动员剂可以通过诱导大量HSC动员进入血液循环来扩大这一过程。该方法在临床上广泛用于治疗血液系统疾病。但是,在生理条件下,迁移后的HSC(称为迁移性HSC)的特性仍未完全表征。在这项研究中,我们调查了迁徙性造血干细胞自我更新,重构和维持BM的能力。我们表明,迁移后,HSC可以稳定地自我更新并保持BM的稳态。然而,虽然稳定地重新填充受辐照者的BM,但在进行连续移植时,迁徙的HSC在淋巴样谱系重建中显示出缺陷。我们的发现为迁移后的HSC特性提供了有趣的知识,这可能有益于基于HSC的疗法对血液学疾病的治疗研究。
更新日期:2021-03-05
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