International Journal of Stem Cells

  • 제16권4호
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  • Pages.385-393
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  • 2023
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  • 2005-3606(pISSN)
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  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
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Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

  • Ju-Hyun Lee (Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine) ;
  • Mohammed R. Shaker (Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine) ;
  • Si-Hyung Park (Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine) ;
  • Woong Sun (Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine)
  • 투고 : 2023.02.09
  • 심사 : 2023.06.20
  • 발행 : 2023.11.30
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초록

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

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과제정보

This research was supported by the Brain Research Program through the National Research Foundation (NRF), funded by the Korean Ministry of Science, ICT, and Future Planning (NRF-2021M3E5D9021368, NRF-2019M3E5D2A01063939, and 2015M3C7A1028790), as well as by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program (IITP-2023-2020-0-01819) supervised by the IITP (Institute for Information & Communications Technology Planning & Evaluation).

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