Mechanism of lung alveolar maturation upon "Birth"

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15463
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Morimoto Mitsuru 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (70544344)
• Co-Investigator(Renkei-kenkyūsha): MATSUOKA CHISA 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 技術補佐員 ; KIKUCHI YUKI 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 大学院生
• Research Collaborator: HASEGAWA KOICHI 京都大学, 呼吸器内科, 大学院生 ; Tsao Po-Nien 国立台湾大学, 医学部, 准教授 ; Cardoso Willington Columbia University, Professor
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 肺胞 / Notchシグナル / オルガノイド

Outline of Final Research Achievements

In this study, we investigated alveolar epithelial Notch signaling deletion mice, which show the emphysema phenotype with within 2 weeks after birth, to elucidate the mechanism of alveolar maturation through Notch signaling during neonatal period. We discovered that Notch signaling is important for postnatal alveolar tissue maturation and in particular type II alveolar epithelium (AT 2) cells are Notch activated cells, indicating that the Notch signaling promoted epithelial tissue expansion by controlling the proliferation and differentiation of AT2 cells as the tissue stem cell. We also identified PDGF-A as a target gene for Notch and showed that it is necessary for the proliferation of myofibroblasts that make alveolar septa. We also established an alveolar organoid culture technique and succeeded in reproducing the Notch deficient phenotype in vitro.

Free Research Field

発生遺伝学