PT  - JOURNAL ARTICLE
AU  - Yuchuan Miao
AU  - Yannis Djeffal
AU  - Alessandro De Simone
AU  - Kongju Zhu
AU  - Andrew Silberfeld
AU  - Jong Gwan Lee
AU  - Jyoti Rao
AU  - Oscar A. Tarazona
AU  - Alessandro Mongera
AU  - Pietro Rigoni
AU  - Margarete Diaz-Cuadros
AU  - Laura Min Sook Song
AU  - Stefano Di Talia
AU  - Olivier Pourquié
TI  - Reconstruction and deconstruction of human somitogenesis in vitro
AID  - 10.1101/2022.05.11.491561
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.11.491561
4099  - http://biorxiv.org/content/early/2022/05/11/2022.05.11.491561.short
4100  - http://biorxiv.org/content/early/2022/05/11/2022.05.11.491561.full
AB  - The body of vertebrates displays a segmental organization which is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric organization is first implemented when somites, which contain the precursors of skeletal muscles and vertebrae, are rhythmically generated from the presomitic mesoderm (PSM). Somites then become subdivided into anterior and posterior compartments essential for vertebral formation and segmental patterning of the peripheral nervous system1–4. How this key somitic subdivision is established remains poorly understood. Here we introduce novel tridimensional culture systems of human pluripotent stem cells (PSCs), called Somitoids and Segmentoids, which can recapitulate the formation of epithelial somite-like structures with antero-posterior (AP) identity. Using these systems, we identified a key organizing function of the segmentation clock in converting temporal rhythmicity into the spatial regularity of anterior and posterior somitic compartments. We show that an initial salt-and-pepper expression pattern of the segmentation gene MESP2 in the newly formed segment is transformed into defined compartments of anterior and posterior identity via an active cell sorting mechanism. Moreover, we demonstrate a large degree of independence of the various patterning modules involved in somitogenesis including the segmentation clock, somite epithelialization and AP polarity patterning. Together we put forward a novel framework accounting for the symmetry breaking process initiating somite polarity patterning. Our work provides a valuable platform to decode general principles of somitogenesis and advance knowledge of human development.Competing Interest StatementThe authors declare the following competing interests: O.P. is scientific founder of Anagenesis Biotechnologies.