Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Curr Biol. 2020 Sep 7;30(17):3316-3329.e5. doi: 10.1016/j.cub.2020.06.027. Epub 2020 Jul 9.
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.
在造血过程中，祖细胞从其环境中接收和解释各种调节信号。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以及与龛位的物理附着方面。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，我们表明整合素在调控控制造血祖细胞行为的细胞信号方面在果蝇造血过程中起着关键作用。整合素可以通过粘着斑激酶 (FAK) 信号直接调节造血作用，也可以通过指导细胞外基质 (ECM) 的组装和/或维持间接调节造血作用。ECM 组织和密度通过调节多个信号通路（包括骨形态发生蛋白 (BMP) 和 Hedgehog (Hh)）来控制血液祖细胞的行为。此外，我们还表明，整合素和 ECM 在感染后减少，这可能有助于激活免疫反应。我们的研究结果提供了对整合素如何塑造造血祖细胞周围信号环境的机制见解。
