![]() ![]() This organization results in a ‘soccer ball-like’, mosaic pattern in which Lgr5+ ISCs form a continuous network that surrounds each Paneth cell 4. ![]() ISCs expressing Lgr5 are intercalated between Paneth cells, which are secretory cells with antibacterial functions. ISCs are not only limited in number and location, but also arranged in a specific pattern. The rapid regeneration of the intestinal epithelium is enabled by fast-cycling Lgr5+ intestinal stem cells (ISCs) crowded into the base of the crypt 1, 2, 3. Reduction of this newly-identified behavior of stem cells could contribute to disease and age-related changes. ![]() This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. Crypt cells then performed a coordinated dilation of the crypt lumen, which resulted in peristalsis-like motion that forced damaged cells out of the crypt. Ablation of one to three cells initiated rapid motion of crypt cells that restored the alternation in the pattern within about two hours with only the rearrangement of pre-existing cells, without any cell division. To study the robustness of the alternating pattern, we used intravital two-photon microscopy in mice with fluorescently-labeled Lgr5+ intestinal stem cells and precisely perturbed the mosaic pattern with femtosecond laser ablation. Despite the continuous renewal and turnover of the small intestinal epithelium, the intestinal crypt maintains a ‘soccer ball-like’, alternating pattern of stem and Paneth cells at the base of the crypt. ![]()
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