Establishment of human airway organoid by understanding airway development in single-cell resolution

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03693
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mitsuru Morimoto 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (70544344)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 呼吸器 / 気道 / 発生学 / 幹細胞 / オルガノイド

Outline of Final Research Achievements

The study examined fetal mouse airway epithelium and mesenchymal tissue differentiation at a single-cell level via scRNA-seq. Key findings include early fate decisions in basal cells at E14.5, driven by TGFb upregulation and subsequent cell proliferation decrease. TGFb signaling induced differentiation, delayed in TGFb receptor-deficient epithelia. Injury studies revealed reversal of developmental dynamics in tissue regeneration. Additionally, distinct origins for tracheal cartilage and smooth muscle were identified. A protocol for inducing tracheal mesenchymal tissue from human ES cells was established. Further research focuses on optimizing co-culturing conditions with epithelial cells.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

この研究成果は、次のような分野への波及効果が期待されます。（１）気道疾患の治療法の開発: 気道上皮および間充織の分化プロセスの理解を深めることで、気道疾患の治療法の開発が可能となります。例えば、気道再生療法や気道再建手術などの治療法に直接応用できます。（２）幹細胞療法の発展: 組織幹細胞や間充織細胞を用いた幹細胞療法の開発に役立ちます。特に、気道再生や肺再生における幹細胞療法の進歩が期待されます。総合的に、本研究は気道および肺の生物学的理解に加えて、疾患治療や再生医療の進歩に向けた重要な基盤を提供することが期待されます。