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

TY - JOUR

T1 - Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis

AU - Gribaudo, Simona

AU - Robert, Rémi

AU - van Sambeek, Björn

AU - Mirdass, Camil

AU - Lyubimova, Anna

AU - Bouhali, Kamal

AU - Ferent, Julien

AU - Morin, Xavier

AU - van Oudenaarden, Alexander

AU - Nedelec, Stéphane

N1 - © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2024/8

Y1 - 2024/8

N2 - 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.

AB - 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.

KW - Humans

KW - Organogenesis

KW - Spinal Cord/embryology

KW - Cell Differentiation

KW - Spine/embryology

KW - Models, Biological

KW - Body Patterning/genetics

KW - Morphogenesis

KW - Pluripotent Stem Cells/cytology

KW - Organoids/growth & development

U2 - 10.1038/s41587-023-01956-9

DO - 10.1038/s41587-023-01956-9

M3 - Article

C2 - 37709912

SN - 1087-0156

VL - 42

SP - 1243

EP - 1253

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 8

ER -