Three-dimensional induction of dorsal, intermediate and ventral spinal cord tissues from human pluripotent stem cells
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ABSTRACT The spinal cord contains more than 20 distinct subclasses of neurons that form well-organized neural circuits capable of sensing the environment and generating motor behavior. Although recent studies have described the efficient in vitro generation of spinal motor neurons, the induction of the spinal cord as a whole tissue has not been achieved. In the present study, we demonstrate three-dimensional (3D) induction of dorsal spinal cord-like tissues from human pluripotent stem cells. Our 3D spinal cord induction (3-DiSC) condition recapitulates patterning of the developing dorsal spinal cord and enables the generation of four types of dorsal interneuron marker-positive cell populations. By activating Shh signaling, intermediate and ventral spinal cord-like tissues are successfully induced. After dissociation of these tissues, somatosensory neurons and spinal motor neurons are detected and express neurotransmitters in an in vivo manner. Our approach provides a useful experimental tool for the analysis of human spinal cord development and will contribute to research on the formation and organization of the spinal cord, and its application to regenerative medicine.
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Components of the cortico-spinal-motor pathway have been generated or studied in isolation, but the in vitro derivation and assembly of this three-part system with human cells had not been achieved.
“Although components of the cortico-spinal-motor pathway have been generated or studied in isolation (Ogura et al., 2018; Sances et al., 2016; Shi et al., 2018; Steinbeck et al., 2016), the in vitro derivation and assembly of this three-part system have not yet been achieved with human cells.”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Ogura et al., 2018
The authors argue that this model surpasses earlier work that made separate motor-circuit components in 3D alone or in 2D co-culture.
“This represents a significant advance beyond prior models in which individual components of motor circuits have been generated in 3D in isolation or co-cultured in 2D (Duval et al., 2019; Ogura et al., 2018; Sances et al., 2016; Shi et al., 2018; Steinbeck et al., 2016).”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Ogura et al., 2018
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Generation of Functional Human 3D Cortico-Motor Assembloids
Andersen, J., Revah, O., Miura, Y., Thom, N., Amin, N. D., Kelley, K. W., Singh, M., Chen, X., Thete, M. V., Walczak, E. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.11.017 · Cited by 593 · see citing works
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BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids
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- Authors
- Ogura, T., Sakaguchi, H., Miyamoto, S., & Takahashi, J.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Sakaguchi, Hideya
- Takahashi, Jun
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2018-07-30
- Volume
- 145
- Issue
- 16
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC6124545
- OpenAlex
- W2883350783
- Cited by
- 183
- References
- 47
- Citations by year
- 2026: 17 · 2025: 29 · 2024: 30 · 2023: 24 · 2022: 29 · 2021: 23 · 2020: 17 · 2019: 11 · 2018: 3
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Development (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- human pluripotent stem cells, dorsal spinal cord, ventral spinal cord, dorsal interneurons, Sonic hedgehog signaling, somatosensory neurons, spinal motoneurons, 3D cell culture, spinal cord development, regenerative medicine
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Embryonic Induction, Female, Humans, Interneurons, Mice, Inbred C57BL, Mice, Transgenic, Motor Neurons, Pregnancy, Spinal Cord, Cell Culture Techniques, Tissue Engineering, Mice, Tissue Scaffolds, Induced Pluripotent Stem Cells
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