Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Curr Opin Hematol. 2022 May 1;29(3):112-118. doi: 10.1097/MOH.0000000000000706. Epub 2022 Feb 7.
Awarding the 2021 Nobel to Ardem Patapoutian for the discovery of the PIEZO mechanotransducers has emphasized the importance of touch-sensing mechanisms in cell physiology. It is well known that PIEZO1 is expressed at the surface of red blood cells where it adjusts their hydration status under mechanical constraints. Besides this, recent findings suggest that PIEZO1 plays a broader role in erythroid lineage. This review aims to actualize the knowledge on PIEZO1 functions all along erythropoiesis.
PIEZO1 is expressed in erythroid progenitors, and controls proliferation and differentiation of nucleated cells, as well as maturation of reticulocytes. As PIEZO1 detects displacements in the range of cell-cell interactions, it might mediate the interaction between the differentiating cells and their microenvironment through an inside-out activation of integrins on human erythroblasts as suggested by in-vitro data. Moreover, PIEZO1 is also expressed at the surface of macrophages where it regulates red blood cells clearance through erythrophagocytosis.
These new findings on PIEZO1 suggest a continuous effect of mechanotransduction all over erythropoiesis from progenitors to clearance of red blood cells. Therefore, they open a new era in the understanding of hereditary xerocytosis pathophysiology, helping identify new potential therapeutic targets for the future.
综述目的:将 2021 年诺贝尔生理学或医学奖授予发现机械门控离子通道 PIEZO 的 Ardem Patapoutian,这强调了触觉感知机制在细胞生理学中的重要性。众所周知,PIEZOl 在红细胞表面表达,在机械约束下调节其水合状态。除此之外,最近的研究结果表明 PIEZO1 在红细胞谱系中发挥着更广泛的作用。本综述旨在阐述 PIEZO1 在整个红细胞生成过程中的功能。
最新发现:PIEZOl 在红细胞祖细胞中表达,控制有核细胞的增殖和分化,以及网织红细胞的成熟。由于 PIEZO1 检测到细胞间相互作用范围内的位移,它可能通过体外数据提示的整联蛋白在人红细胞上的内-外激活,介导分化细胞与其微环境之间的相互作用。此外,PIEZOl 也在巨噬细胞表面表达,通过红细胞吞噬作用调节红细胞的清除。
总结:这些关于 PIEZO1 的新发现表明,机械转导在从祖细胞到清除红细胞的整个红细胞生成过程中都有连续的作用。因此,它们开创了一个理解遗传性红细胞增多症病理生理学的新时代,有助于为未来确定新的潜在治疗靶点。