Blood flow-related mechanical stress transduction mechanism during endothelial-to-hematopoietic transition

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06692
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kyushu University
• Principal Investigator: Sato Yuki 九州大学, 医学研究院, 准教授 (90508186)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 内皮－造血転換 / アクアポリン / 液胞

Outline of Final Research Achievements

Hematopoietic stem cells are generated during embryogenesis by transdifferentiation of endothelial cells in the dorsal aorta. A specific cell population that is released from the blood vessels during this process migrates into the bloodstream to the bone marrow, where they are maintained as hematopoietic stem cells. Elucidation of the mechanisms underlying endothelial-to-hematopoietic transition is an important issue directly related to the understanding of the origin of hematopoietic stem cells and therapeutic regulation of the hematopoiesis. In this study, we proved that water permeation into the cell via the water channel Aquaporin (AQP) is a direct cause of the cell rounding that occurs during the endothelial-to-hematopoietic transition. Our study also suggested that a group of mechanical stress-activated TRP channel molecules may be involved in this process.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

内皮－造血転換過程において、血管から生み出された造血幹細胞が多分化能を獲得する際に働く分子メカニズムは解明されつつある。一方でなぜ内皮－造血転換を起こす細胞が特定の血管部位に限定されているのか、また扁平な血管内皮細胞を球状の造血幹細胞へと変化させる際に直接的に働く分子機構は未解明であった。本研究から、水チャネル分子AQPを介して血管内の水分子を細胞内へ取り込むことにより細胞が球形化することが判明した。この発見をきっかけに、今後、mechanophysioloyの観点からの造血現象理解が進むことが期待される。