Reconstituting human somitogenesis in vitro.

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Human Embryogenesis

Background:

• Vertebrate segmentation, crucial for development, is poorly understood in humans due to limitations.
• Existing human pluripotent stem cell models struggle to recapitulate somitogenesis accurately in space and time.

Purpose of the Study:

• To develop a robust 3D model for studying human segmentation and somitogenesis.
• To investigate the molecular mechanisms underlying somite formation and stabilization.
• To explore the potential of this model for studying congenital spine diseases.

Main Methods:

• Development of a pluripotent stem cell-derived mesoderm-based 3D model termed 'axioloid'.
• Analysis of oscillatory dynamics of the segmentation clock, morphological and molecular characteristics.
• Investigation of signaling pathways including FGF-WNT and retinoic acid.
• Comparative analysis with human embryos and use of patient-derived induced pluripotent stem cells.

Main Results:

• Axioloids accurately recapitulate human segmentation clock dynamics and somite formation in vitro.
• The model exhibits correct rostrocaudal patterning and signaling gradients (FGF-WNT, retinoic acid).
• Retinoic acid signaling plays a critical role in segment stabilization, interacting with the extracellular matrix.
• Axioloids show high similarity to human embryos, including Hox code expression.
• The model successfully demonstrated disease modeling for congenital spine diseases using patient-derived iPSCs.

Conclusions:

• Axioloids provide a powerful new platform for studying human axial development and somitogenesis in vitro.
• The model elucidates the role of retinoic acid in somite stabilization and epithelialization.
• Axioloids are valuable for investigating the pathogenesis of human congenital spine diseases and for drug screening.