Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion

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.

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“…The critical task at hand is determining whether this activation ultimately correlates with behavioral changes, such as motor function decline in PD models, especially during periods relevant to human aging. We expect that advancements in technology, including the utilization of recent stem cell or organoid models to simulate the onset and progression of PD, 56 , 57 , 58 along with the incorporation of human glial cells, 59 will facilitate studies in uncovering more precise mechanisms in the future. Our study established α-Syn as a preexisting risk factor for the exacerbation of PD progression induced by SARS-CoV-2 infection.…”

Signaling pathways in colorectal cancer: implications for the target therapies

“…Two cell lines, human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been used to generate colonic organoid [247]. Peripheral neuron-organoid interactions play roles in the development of colonic epithelial cells, specifically of colon enterochromaffin cells, an inter-organ interaction in organ development [248], and non-synaptic substance P which not only contains in cerebrospinal fluid but also the cells of peripheral tissue, plays an important role during this process [249,250].…”