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首页> 外文期刊>Stem Cells >Wnt3a activates dormant c-Kit(-) bone marrow-derived cells with short-term multilineage hematopoietic reconstitution capacity.
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Wnt3a activates dormant c-Kit(-) bone marrow-derived cells with short-term multilineage hematopoietic reconstitution capacity.

机译：Wnt3a激活具有短期多谱系造血重建能力的休眠c-Kit（-）骨髓来源的细胞。

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摘要

Quiescent cells lacking expression of mature lineage makers and the c-Kit receptor reside in adult bone marrow. Despite their phenotypic similarity to hematopoietic stem cells, these Lin(-)Sca-1(+)c-Kit(-) cells lack myeloid and erythroid potential and long-term hematopoietic repopulating capacity, whereas, recent studies have functionally demonstrated that the Lin(-)Sca-1(+)c-Kit(-) population contains early lymphoid-committed progenitors. Examining the role of Wnt signaling in regulation of this population, we found that c-Kit(-) cells express diverse Wnt receptors and proliferate upon Wnt pathway activation in vitro and in vivo. Stimulation with Wnt3a, but not Wnt5a or Wnt11, promoted c-Kit(-) cells to give rise to myeloid and erythroid progenitors with robust self-renewal capacity measured by clonal replating. In addition, Wnt3a-stimulated c-Kit(-) cells gave rise to all hematopoietic lineages (lymphoid, myeloid, and erythroid) upon transplant into the liver of newborn recipient mice. Our study reveals that Wnt3a activates unique cell fate decisions of dormant c-Kit(-) that promotes short-term multilineage reconstitution capacity in vivo, thereby revealing a unique role for Wnt activation in hematopoiesis. Overall, our results highlight the potential of utilizing signaling molecules known to have instructive roles in regeneration to discover cell subsets residing in adult organisms with unexploited regenerative capacity.
机译：缺乏成熟谱系生成物表达的静态细胞，而c-Kit受体位于成年骨髓中。尽管它们与造血干细胞在表型上相似，但这些Lin（-）Sca-1（+）c-Kit（-）细胞缺乏髓样和类红血球潜力以及长期的造血繁殖能力，而最近的研究已从功能上证明了Lin （-）Sca-1（+）c-Kit（-）群体包含早期淋巴细胞样祖细胞。检查Wnt信号在调节这一人群中的作用，我们发现c-Kit（-）细胞表达不同的Wnt受体，并在体外和体内激活Wnt途径后增殖。用Wnt3a而不是Wnt5a或Wnt11刺激，可促进c-Kit（-）细胞产生具有髓系和红系祖细胞，并具有通过克隆重铺测量的强大的自我更新能力。此外，Wnt3a刺激的c-Kit（-）细胞移植到新生受体小鼠的肝脏中后会引起所有造血谱系（淋巴，髓样和类红细胞）。我们的研究表明Wnt3a激活了休眠c-Kit（-）的独特细胞命运决定，该决定促进了体内短期多谱系重建能力，从而揭示了Wnt激活在造血中的独特作用。总的来说，我们的研究结果突出了利用已知在再生中具有指导作用的信号分子潜在地发现存在于未利用的再生能力的成年生物中的细胞亚群的潜力。

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