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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

8 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
TijdschriftNature Biotechnology
DOI's
StatusE-pub ahead of print - 14 sep. 2023

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