Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis

Simona Gribaudo, Rémi Robert, Björn van Sambeek, Camil Mirdass, Anna Lyubimova, Kamal Bouhali, Julien Ferent, Xavier Morin, Alexander van Oudenaarden, Stéphane Nedelec

Research output: Contribution to journal/periodicalArticleScientificpeer-review

8 Citations (Scopus)

Abstract

Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. Here we report the generation of human trunk-like structures that model the co-morphogenesis, patterning and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single-cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into a neural tube surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms, which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue co-morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.

Original languageEnglish
JournalNature Biotechnology
DOIs
Publication statusE-pub ahead of print - 14 Sept 2023

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