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発表内容

Title:

Single-cell transcriptome and morphogenesis of developing airways

 

Speaker:

Mitsuru Morimoto

RIKEN BDR, Lab. for Lung Development and Regeneration

 

Abstract:

The physiological function of the organ is engaged in specialized cell types and unique tissue structure developed during embryogenesis, yet spatiotemporal coordination between cell differentiation and tissue morphogenesis is not clear. In this seminar, I would like to talk about single-cell resolution analyses for developing mouse respiratory system, specify airways. Using single-cell RNA sequencing, we revealed the dynamic transitions from uniformed progenitors to mature cells acquiring the heterogeneity and molecular mechanism of airway stem cell development. We identified that Tgfß and Notch signaling coordinate proper timing of stem cell selection and acquisition of quiescence. Some of developmental mechanism of stem cell regulation was conserved in adult tissue regeneration. We also identified the origin of airway mesenchyme that generates cartilage and smooth muscle and related with human congenital defects such as tracheoesophageal fistula and tracheal agenesis. Bidirectional canonical Wnt signaling between endodermal-and-mesodermal around E9.5 induces airway mesenchymal progenitors in mouse splanchnic mesoderm. Furthermore, In vitro, activating Wnt and Bmp signaling in mouse ES cell (ESC)-derived lateral plate mesoderm (LPM) generated airway mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation was required along with Wnt to generate authentic airway mesoderm. These findings are foundations for deriving human airway mesoderm for applications in tracheal tissue repair.

 

References:

Kishimoto et al., Nature Communications 2018

Kishimoto et al., bioRxiv 2020, doi: https://doi.org/10.1101/758235