Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
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DOI：
10.1182/blood-2011-01-328567
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Mercher, Thomas
中科院分区：
文献类型：
--
作者：
Cornejo, Melanie G.;Mabialah, Vinciane;Mercher, Thomas
NOTCH 信号通路涉及广泛的发育过程，包括细胞命运决定。然而，其在干细胞谱系定型的不同步骤中发挥作用的分子基础尚不清楚。我们最近发现NOTCH信号通路是造血过程中巨核细胞谱系规范的正调节因子，但允许造血干细胞分化为红巨核细胞谱系的发育途径仍然存在争议。在这里，我们研究了 NOTCH 下游介质在巨核细胞生成过程中的作用，并报告了 NOTCH 和 PI3K/AKT 通路之间的串扰。我们证明了磷酸酶与张力蛋白同源物和 Forkhead Box O 类因子对体内巨核细胞生成的抑制作用。最后，我们的数据注释了造血系统中的发育机制，使得能够在造血干细胞或定型祖细胞水平上做出决定以定型为巨核细胞谱系，支持两种不同的发育途径的存在。 （血。2011；118(5):1264-1273）
The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways. (Blood. 2011;118(5):1264-1273)