International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion

  • Young Hyun Che (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • In Young Choi (The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine) ;
  • Chan Eui Song (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Chulsoo Park (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Seung Kwon Lim (Department of Medicine, Graduate School, Kyung Hee University) ;
  • Jeong Hee Kim (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Su Haeng Sung (Department of Pathology, College of Medicine, Kyung Hee University) ;
  • Jae Hoon Park (Department of Pathology, College of Medicine, Kyung Hee University) ;
  • Sun Lee (Department of Pathology, College of Medicine, Kyung Hee University) ;
  • Yong Jun Kim (Department of Biomedical Science, Graduate School, Kyung Hee University)
  • Received : 2023.03.08
  • Accepted : 2023.04.06
  • Published : 2023.08.30
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Abstract

Background and Objectives: The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids. Methods and Results: Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheral neurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms. Conclusions: Our results suggest that the peripheral nervous system may have a significant role in the development of colonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF-2022M3A9H1016308, NRF-2022R1F1A1066611, NRF-2023R1A2C2007120), the Ministry of SMEs and startups (S3098634), the Korean Fund for Regenerative Medicine (2021M3E5E5096744), and the KIST Institutional Program (Project No.2Z05790-19-037).

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