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Integrins Modulate Extracellular Matrix Organization to Control Cell Signaling during Hematopoiesis.
Current Biology ( IF 8.1 ) Pub Date : 2020-07-09 , DOI: 10.1016/j.cub.2020.06.027
Rohan J Khadilkar 1 , Kevin Y L Ho 1 , Bhavya Venkatesh 1 , Guy Tanentzapf 1
Affiliation  

During hematopoiesis, progenitor cells receive and interpret a diverse array of regulatory signals from their environment. These signals control the maintenance of the progenitors and regulate the production of mature blood cells. Integrins are well known in vertebrates for their roles in hematopoiesis, particularly in assisting in the migration to, as well as the physical attachment of, progenitors to the niche. However, whether and how integrins are also involved in the signaling mechanisms that control hematopoiesis remains to be resolved. Here, we show that integrins play a key role during fly hematopoiesis in regulating cell signals that control the behavior of hematopoietic progenitors. Integrins can regulate hematopoiesis directly, via focal adhesion kinase (FAK) signaling, and indirectly, by directing extracellular matrix (ECM) assembly and/or maintenance. ECM organization and density controls blood progenitor behavior by modulating multiple signaling pathways, including bone morphogenetic protein (BMP) and Hedgehog (Hh). Furthermore, we show that integrins and the ECM are reduced following infection, which may assist in activating the immune response. Our results provide mechanistic insight into how integrins can shape the signaling environment around hematopoietic progenitors.



中文翻译:

整合素调节细胞外基质组织以控制造血过程中的细胞信号传导。

在造血过程中,祖细胞接收并解释来自其环境的各种调节信号。这些信号控制祖细胞的维持并调节成熟血细胞的产生。整合素在脊椎动物中因其在造血中的作用而广为人知,特别是在协助祖细胞迁移到生态位以及祖细胞与生态位的物理连接方面。然而,整合素是否以及如何参与控制造血的信号机制仍有待解决。在这里,我们表明整合素在果蝇造血过程中在调节控制造血祖细胞行为的细胞信号中发挥关键作用。整联蛋白可以通过粘着斑激酶 (FAK) 信号直接和间接调节造血功能,通过指导细胞外基质 (ECM) 组装和/或维护。ECM 组织和密度通过调节多种信号通路来控制血液祖细胞的行为,包括骨形态发生蛋白 (BMP) 和刺猬 (Hh)。此外,我们表明整合素和 ECM 在感染后减少,这可能有助于激活免疫反应。我们的结果提供了关于整合素如何塑造造血祖细胞周围信号环境的机制洞察。

更新日期:2020-09-08
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