Abstract

Jose Lemme-Dumit works in the field of mucosal immunology and vaccines. In this mSphere of Influence article, he reflects on how two papers, "Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium" by Sato et al. (T. Sato, D. E. Stange, M. Ferrante, R. G. J. Vries, et al., Gastroenterology 141:1762-1772, 2011, https://doi.org/10.1053/j.gastro.2011.07.050) and "T helper cell cytokines modulate intestinal stem cell renewal and differentiation" by Biton et al. (M. Biton, A. L. Haber, N. Rogel, G. Burgin, et al., Cell 175:1307-1320.E22, 2018, https://doi.org/10.1016/j.cell.2018.10.008), have influenced his research by describing the development of intestinal organoid cultures and implementation of high-throughput sequencing analysis. The combination of these forefront technologies has expanded opportunities for mechanistic interrogation of host immunity to enteric pathogens.

Highlights

  • Homeostasis and host defenses in the human gut are finely regulated

  • The intestinal epithelium provides a physiological and immunological barrier that protects the host from pathogens and harmful agents while maintaining a peaceful coexistence with nutrients and the gut microbiota

  • The authors found that gastrin and nicotinamide improved culture efficiency, with nicotinamide being essential for prolonging culture viability for up to 1 month

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Summary

Introduction

Homeostasis and host defenses in the human gut are finely regulated. The intestinal epithelium provides a physiological and immunological barrier that protects the host from pathogens and harmful agents while maintaining a peaceful coexistence with nutrients and the gut microbiota. This breakthrough transformed tissue culture technologies by enabling the generation of three-dimensional (3D) self-organizing tissue structures that recapitulate critical features of the human intestinal epithelium in vivo. Self-renewal of the intestinal epithelium requires distinct proliferative signals on crypt intestinal stem cells.

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