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Modeling Human Paraxial Mesoderm Development with Pluripotent Stem Cells.

Yuchuan Miao1,2, Margarete Diaz-Cuadros1,3, Olivier Pourquié1,2,4

  • 1Department of Genetics, Harvard Medical School, Boston, MA, USA.

Methods in Molecular Biology (Clifton, N.J.)
|October 16, 2023
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Human pluripotent stem cells model early embryonic development. New protocols reveal insights into the segmentation clock and somitogenesis, advancing developmental biology research.

Keywords:
Directed differentiationHuman developmentOrganoidParaxial mesodermPluripotent stem cellSomiteSomitogenesisThe segmentation clock

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genetics

Background:

  • Paraxial mesoderm segmentation into somites is crucial for vertebrate body plan organization.
  • The segmentation clock, an oscillating gene regulatory network, controls rhythmic somite formation.
  • Studying human somitogenesis is challenging due to limited embryo access and ethical constraints.

Purpose of the Study:

  • To develop in vitro models for studying human paraxial mesoderm development.
  • To investigate the dynamics of the human segmentation clock.
  • To recapitulate key features of somitogenesis using human pluripotent stem cell-derived models.

Main Methods:

  • Established a 2D cell monolayer system to model the human segmentation clock.
  • Developed a 3D organoid system ('somitoid') for simultaneous somite-like structure formation.
  • Created another organoid system ('segmentoid') to reconstitute in vivo-like somitogenesis hallmarks.

Main Results:

  • The 2D system successfully recapitulated the dynamics of the human segmentation clock.
  • The 'somitoid' organoids demonstrated simultaneous formation of somite-like structures.
  • The 'segmentoid' organoids exhibited in vivo-like characteristics of somitogenesis.

Conclusions:

  • Complementary in vitro model systems using human pluripotent stem cells advance the study of somitogenesis.
  • These models provide a powerful platform to decode human developmental biology processes.
  • The developed protocols facilitate research into early human embryonic development.