Production of human spinal-cord organoids recapitulating neural-tube morphogenesis

Ju Hyun Lee; Hyogeun Shin; Mohammed R. Shaker; Hyun Jung Kim; Si Hyung Park; June Hoan Kim; Namwon Lee; Minjin Kang; Subin Cho; Tae Hwan Kwak; Jong Woon Kim; Mi Ryoung Song; Seung Hae Kwon; Dong Wook Han; Sanghyuk Lee; Se Young Choi; Im Joo Rhyu; Hyun Kim; Dongho Geum; Il Joo Cho; Woong Sun

doi:10.1038/s41551-022-00868-4

Production of human spinal-cord organoids recapitulating neural-tube morphogenesis

Ju Hyun Lee, Hyogeun Shin, Mohammed R. Shaker, Hyun Jung Kim, Si Hyung Park, June Hoan Kim, Namwon Lee, Minjin Kang, Subin Cho, Tae Hwan Kwak, Jong Woon Kim, Mi Ryoung Song, Seung Hae Kwon, Dong Wook Han, Sanghyuk Lee, Se Young Choi, Im Joo Rhyu, Hyun Kim, Dongho Geum, Il Joo ChoWoong Sun

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects.

Original language	English
Pages (from-to)	435-448
Number of pages	14
Journal	Nature Biomedical Engineering
Volume	6
Issue number	4
DOIs	https://doi.org/10.1038/s41551-022-00868-4
Publication status	Published - 2022 Apr

ASJC Scopus subject areas

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41551-022-00868-4

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Lee, J. H., Shin, H., Shaker, M. R., Kim, H. J., Park, S. H., Kim, J. H., Lee, N., Kang, M., Cho, S., Kwak, T. H., Kim, J. W., Song, M. R., Kwon, S. H., Han, D. W., Lee, S., Choi, S. Y., Rhyu, I. J., Kim, H., Geum, D., ... Sun, W. (2022). Production of human spinal-cord organoids recapitulating neural-tube morphogenesis. Nature Biomedical Engineering, 6(4), 435-448. https://doi.org/10.1038/s41551-022-00868-4

Lee, JH, Shin, H, Shaker, MR, Kim, HJ, Park, SH, Kim, JH, Lee, N, Kang, M, Cho, S, Kwak, TH, Kim, JW, Song, MR, Kwon, SH, Han, DW, Lee, S, Choi, SY, Rhyu, IJ, Kim, H, Geum, D, Cho, IJ & Sun, W 2022, 'Production of human spinal-cord organoids recapitulating neural-tube morphogenesis', Nature Biomedical Engineering, vol. 6, no. 4, pp. 435-448. https://doi.org/10.1038/s41551-022-00868-4

@article{149ac3555d4d4ce89183602ea900e4da,

title = "Production of human spinal-cord organoids recapitulating neural-tube morphogenesis",

abstract = "Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects.",

author = "Lee, {Ju Hyun} and Hyogeun Shin and Shaker, {Mohammed R.} and Kim, {Hyun Jung} and Park, {Si Hyung} and Kim, {June Hoan} and Namwon Lee and Minjin Kang and Subin Cho and Kwak, {Tae Hwan} and Kim, {Jong Woon} and Song, {Mi Ryoung} and Kwon, {Seung Hae} and Han, {Dong Wook} and Sanghyuk Lee and Choi, {Se Young} and Rhyu, {Im Joo} and Hyun Kim and Dongho Geum and Cho, {Il Joo} and Woong Sun",

note = "Funding Information: We would like to thank the Korea Basic Science Institute, Korea Brain Research Institute, K.-S. Yang and J. Na for their technical support. We especially thank SCREEN Holdings (Kyoto, Japan) and Kim & Friends (Seoul, Republic of Korea) for technical support utilizing the OCT instrument, Cell3iMager Estier. We also thank J. Hosung (Yonsei University) for his critical comments. This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT and Future Planning (NRF-2015M3C7A1028790, NRF-2017M3C7A1047654, NRF-2017M3A9B3061308 and NRF-2021M3E5D9021368). Funding Information: We would like to thank the Korea Basic Science Institute, Korea Brain Research Institute, K.-S. Yang and J. Na for their technical support. We especially thank SCREEN Holdings (Kyoto, Japan) and Kim & Friends (Seoul, Republic of Korea) for technical support utilizing the OCT instrument, Cell3iMager Estier. We also thank J. Hosung (Yonsei University) for his critical comments. This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT and Future Planning (NRF-2015M3C7A1028790, NRF-2017M3C7A1047654, NRF-2017M3A9B3061308 and NRF-2021M3E5D9021368). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

month = apr,

doi = "10.1038/s41551-022-00868-4",

language = "English",

volume = "6",

pages = "435--448",

journal = "Nature Biomedical Engineering",

issn = "2157-846X",

publisher = "Nature Publishing Group",

number = "4",

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TY - JOUR

T1 - Production of human spinal-cord organoids recapitulating neural-tube morphogenesis

AU - Lee, Ju Hyun

AU - Shin, Hyogeun

AU - Shaker, Mohammed R.

AU - Kim, Hyun Jung

AU - Park, Si Hyung

AU - Kim, June Hoan

AU - Lee, Namwon

AU - Kang, Minjin

AU - Cho, Subin

AU - Kwak, Tae Hwan

AU - Kim, Jong Woon

AU - Song, Mi Ryoung

AU - Kwon, Seung Hae

AU - Han, Dong Wook

AU - Lee, Sanghyuk

AU - Choi, Se Young

AU - Rhyu, Im Joo

AU - Kim, Hyun

AU - Geum, Dongho

AU - Cho, Il Joo

AU - Sun, Woong

N1 - Funding Information: We would like to thank the Korea Basic Science Institute, Korea Brain Research Institute, K.-S. Yang and J. Na for their technical support. We especially thank SCREEN Holdings (Kyoto, Japan) and Kim & Friends (Seoul, Republic of Korea) for technical support utilizing the OCT instrument, Cell3iMager Estier. We also thank J. Hosung (Yonsei University) for his critical comments. This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT and Future Planning (NRF-2015M3C7A1028790, NRF-2017M3C7A1047654, NRF-2017M3A9B3061308 and NRF-2021M3E5D9021368). Funding Information: We would like to thank the Korea Basic Science Institute, Korea Brain Research Institute, K.-S. Yang and J. Na for their technical support. We especially thank SCREEN Holdings (Kyoto, Japan) and Kim & Friends (Seoul, Republic of Korea) for technical support utilizing the OCT instrument, Cell3iMager Estier. We also thank J. Hosung (Yonsei University) for his critical comments. This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT and Future Planning (NRF-2015M3C7A1028790, NRF-2017M3C7A1047654, NRF-2017M3A9B3061308 and NRF-2021M3E5D9021368). Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022/4

Y1 - 2022/4

N2 - Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects.

AB - Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects.

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U2 - 10.1038/s41551-022-00868-4

DO - 10.1038/s41551-022-00868-4

M3 - Article

C2 - 35347276

AN - SCOPUS:85127234262

SN - 2157-846X

VL - 6

SP - 435

EP - 448

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 4

ER -

Production of human spinal-cord organoids recapitulating neural-tube morphogenesis

Abstract

ASJC Scopus subject areas

UN SDGs

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