Aquaporin regulates cell rounding through vacuole formation during endothelial-to-hematopoietic transition
Aquaporin regulates cell rounding through vacuole formation during endothelial-to-hematopoietic transition
复制标题
水通道蛋白在内皮向造血转化过程中通过液泡形成调节细胞变圆
DOI：
10.1101/2022.09.03.506460
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发表时间：
2023
期刊：
影响因子：
4.6
通讯作者：
Sakamoto Hirotaka
中科院分区：
文献类型：
--
作者：
Sato Yuki;Shigematsu Mugiho;Shibata-Kanno Maria;Maejima Sho;Tamura Chie;Sakamoto Hirotaka
内皮细胞向造血细胞转化（EHT）是造血干细胞生成的关键。在EHT期间，生血内皮细胞（HEC）的形态从扁平和粘附的造血细胞变为球形，从背主动脉脱离。HEC在细胞粘附终止前以不依赖于有丝分裂的方式获得圆形形状，这表明非典型的细胞变圆机制。然而，EHT过程中细胞形态变化的直接机制尚不清楚。在这里，我们表明，大的空泡是瞬时形成的禽内皮细胞，水通道蛋白1（AQP 1）定位于空泡和质膜。AQP 1在非HEC中的过表达诱导异位空泡扩张，细胞变圆，随后细胞从内皮脱离进入血流，模拟EHT。HEC中CRISPR/Cas9基因编辑导致的多余AQP功能的丧失阻碍了形态学EHT。我们的研究结果提供了第一个证据表明，造血细胞从内皮细胞的形态分离是由水流入空泡调节。这些发现为进一步探索细胞/组织形态发生的机制提供了重要的见解。
Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical hematopoietic cells, which detach from the dorsal aorta. HECs attain a rounded shape in a mitosis-independent manner before cell adhesion termination, suggesting an atypical cell-rounding mechanism. However, the direct mechanisms underlying this change in cell morphology during EHT remain unclear. Here, we show that large vacuoles were transiently formed in avian HECs, and that aquaporin 1 (AQP1) was localized in the vacuole and plasma membranes. Overexpression of AQP1 in non-HECs induced ectopic vacuole expansion, cell rounding and subsequent cell detachment from the endothelium into the bloodstream, mimicking EHT. Loss of redundant AQP functions by CRISPR/Cas9 gene editing in HECs impeded the morphological EHT. Our findings provide the first evidence to indicate that morphological segregation of hematopoietic cells from endothelial cells is regulated by water influx into vacuoles. These findings provide important insights for further exploration of the mechanisms underlying cell/tissue morphogenesis through water-adoptive cellular responses.