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KMID : 1204720230160030269
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International Journal of Stem Cells
2023 Volume.16 No. 3 p.269 ~ p.280
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Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion
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Che Young-Hyun
Choi In-Young
Song Chan-Eui
Park Chul-Soon
Chee Young-Joon
Kim Jeong-Hee
Sung Su-Haeng
Park Jae-Hoon
Lee Sun
Kim Yong-Jun
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Abstract
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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.
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KEYWORD
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Organogenesis, Colonic organoid, Gut development, Peripheral neuron, Inter-organ crosstalk, Pluripotent stem cell
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