| Autor: |
Kishimoto, Keishi, Furukawa, Kana T., LuzMadrigal, Agustin, Yamaoka, Akira, Matsuoka, Chisa, Habu, Masanobu, Alev, Cantas, Zorn, Aaron M., Morimoto, Mitsuru |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/758235 |
| Popis: |
The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformation results in serious respiration defects in neonates. To establish a human tracheal mesodermal development model, an in vitro differentiation protocol from pluripotent stem cells was desired. Here we show that endodermal-to-mesodermal canonical Wnt signaling induces trachea progenitors in mouse splanchnic mesoderm. Loss of β-catenin in fetal mouse mesoderm caused loss of Tbx4 + tracheal mesoderm and trachea cartilage agenesis. We found that endodermal Wnt ligands promote mesodermal Tbx4 expression independent of known Nkx2.1-mediated respiratory endoderm development. In vitro , activating Wnt and Bmp signaling in mouse ES cell (ESC)-derived lateral plate mesoderm (LPM) generated tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation was required along with Wnt to generate authentic tracheal mesoderm. These findings are foundations for deriving human tracheal mesoderm for applications in tracheal tissue repair. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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