Yuchuan Miao, PhD

Pronouns

He/Him/His

Job Title

Postdoc research fellow

Academic Rank

Research Fellow

Department

Pathology

Authors

Yuchuan Miao, Olivier Pourquie

Principal Investigator

Olivier Pourquie

Research Category: Regenerative Medicine

Tags

Reconstructing human somitogenesis with stem cells

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Scientific Abstract

The metameric organization of vertebrates is first implemented when somites, which contain the precursors of skeletal muscles and vertebrae, are rhythmically generated. This process of somitogenesis is vital for body plan development, yet very little is known about human somitogenesis given limited access to early embryos and ethical concerns. Stem-cell based embryo models provide a promising alternative to in vivo studies. Here we introduce two novel 3D culture systems of human PSCs, called Somitoids and Segmentoids, which can recapitulate the formation of epithelial somite-like structures. Somitoids recapitulate the temporal sequence of somitogenesis, with all cells undergoing differentiation and morphogenesis in a synchronous manner. This system can provide unlimited amounts of cells precisely synchronized in their differentiation and will allow exploring these patterning processes at an unprecedented level of detail. On the other hand, Segmentoids reconstruct the spatio-temporal features of somitogenesis, including gene expression dynamics, tissue elongation, sequential somite morphogenesis, and antero-posterior polarity patterning. They therefore provide an excellent proxy to study human somitogenesis. Together, these two complimentary models provide a valuable platform to decode general principles of somitogenesis, advance knowledge of human development, and promote tissue engineering for regenerative medicine.

Lay Abstract

Somites in early embryos give rise to our vertebrates and muscles, and malformation in their development leads to congenital diseases such as scoliosis. It is impossible to directly study them since their formation occurs between 3 to 4 weeks post conception. Here we use human stem cells to build embryonic somites in the dish. We have successfully established two systems, called Somitoid and Segmentoid, that can recapitulate the dynamics of this process. With these technologies, we are now able to gain knowledge of human development, investigate causes of congenital diseases, and engineer functional tissues for cell therapies.

Clinical Implications

Our stem cell-based technologies allow studying human somite formation, bypassing the lack of access to early human embryos. These allow us to investigate the etiology of diseases such as congenital scoliosis and engineer somite derivatives including muscle, tendon, cartilage, etc.