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Status |
Public on Aug 31, 2023 |
Title |
Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis [scRNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. 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 neural tubes 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 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.
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Overall design |
Single-cell RNA-sequencing analyses were performed on 26 pooled trunk organoids at day 7 of differentiation. Libraries were prepared following 10X Chromium Next GEM Single cell 3' v.3.1 manufacturer protocol. For the spatial transcriptomic study (Tomo-sequecing), two human trunk organoids at day 7, were freshly frozen and then sectioned. Each section was sequenced by bulk RNA sequencing. Libraries were prepared using Cel-Seq2 protocol and Illumina TruSeq small RNA adapters (RPI series).
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Contributor(s) |
Gribaudo S, Robert R, van Sambeek B, Mirdass C, Lyubimova A, Bouhali K, Ferrent J, Morin X, van Oudenaarden A, Nedelec S |
Citation(s) |
37709912 |
Submission date |
Oct 18, 2022 |
Last update date |
Dec 01, 2023 |
Contact name |
Stephane NEDELEC |
E-mail(s) |
stephane.nedelec@inserm.fr
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Organization name |
Institut du Fer à Moulin
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Lab |
Stem cells and Neurodevelopment
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Street address |
17 rue du fer a moulin
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City |
PARIS |
ZIP/Postal code |
75005 |
Country |
France |
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Platforms (1) |
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Samples (1) |
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This SubSeries is part of SuperSeries: |
GSE215983 |
Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis. |
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Relations |
BioProject |
PRJNA891643 |