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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Transient beta-catenin stabilization modifies lineage output from human thymic CD34+CD1a- progenitors.
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Transient beta-catenin stabilization modifies lineage output from human thymic CD34+CD1a- progenitors.

机译：瞬时β-连环蛋白稳定作用可改变人胸腺CD34 + CD1a-祖细胞的谱系输出。

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摘要

Increasing evidence includes Wnt proteins inside the group of master-signaling pathways that govern immune and nonimmune differentiation systems, fundamental for normal development and homeostasis. Although their precise functions in bone marrow and thymus are still controversial, numerous studies have shown that Wnt signaling is able to control the proliferation of hematopoietic stem cells and thymic progenitors and might also affect their cell-fate decisions and subsequent maturation. In the present work, we analyze the effect of transient stimulation of the canonical Wnt pathway in the differentiation potential of Lin(-)CD34(+) CD1a(-) human thymic progenitors, a multipotent and heterogeneous cell population that has the capacity to develop into T cells, NK cells, monocytes, cDC, and pDC. Our results demonstrate that giving a boost to canonical Wnt signaling, triggered by transient exposure to Wnt3a or LiCl, the differentiation capacity of thymic progenitors changes, enhancing NK cell production. On the contrary, Wnt3a- or LiCl-pretreated thymic progenitors generate a significantly lower number of myeloid lineage cells, monocytes, and cDC and exhibit a reduced capacity to differentiate into pDC lineage. As a possible mechanism for this effect, we show that Wnt3a- and LiCl-pretreated progenitors change their membrane levels of receptors for cytokines pivotal for their expansion and differentiation, such as Flt3L. Moreover, canonical Wnt pathway stimulation modifies the transcription factor profile of CD34(+)CD1(-) thymocytes, increasing Hes-1 and ID3 expression levels.
机译：越来越多的证据包括在控制免疫和非免疫分化系统的主信号通路组中的Wnt蛋白，这是正常发育和体内平衡的基础。尽管它们在骨髓和胸腺中的确切功能仍存在争议，但许多研究表明，Wnt信号能够控制造血干细胞和胸腺祖细胞的增殖，还可能影响它们的细胞命运决定和随后的成熟。在目前的工作中，我们分析了瞬时Wnt通路刺激对Lin（-）CD34（+）CD1a（-）人胸腺祖细胞（具有发育能力的多能和异质细胞群体）分化潜能的影响。进入T细胞，NK细胞，单核细胞，cDC和pDC。我们的结果表明，通过短暂暴露于Wnt3a或LiCl触发经典Wnt信号传导，胸腺祖细胞的分化能力会发生变化，从而增强NK细胞的产量。相反，经过Wnt3a或LiCl预处理的胸腺祖细胞产生的髓系谱系细胞，单核细胞和cDC明显减少，并且分化为pDC谱系的能力降低。作为此效应的可能机制，我们表明Wnt3a和LiCl预处理的祖细胞会改变其细胞膜受体的膜水平，这些受体的细胞因子对于其扩张和分化至关重要，例如Flt3L。此外，规范的Wnt途径刺激修饰CD34（+）CD1（-）胸腺细胞的转录因子谱，增加Hes-1和ID3表达水平。

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