Title | Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Choi, J, Rakhilin, N, Gadamsetty, P, Joe, DJ, Tabrizian, T, Lipkin, SM, Huffman, DM, Shen, X, Nishimura, N |
Journal | Sci Rep |
Volume | 8 |
Issue | 1 |
Pagination | 10989 |
Date Published | 2018 Jul 20 |
ISSN | 2045-2322 |
Abstract | 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. 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. 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. 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. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Reduction of this newly-identified behavior of stem cells could contribute to disease and age-related changes. |
DOI | 10.1038/s41598-018-29230-y |
Alternate Journal | Sci Rep |
PubMed ID | 30030455 |
PubMed Central ID | PMC6054609 |
Grant List | P30 AG038072 / AG / NIA NIH HHS / United States R01 GM114254 / GM / NIGMS NIH HHS / United States R56 AG052981 / AG / NIA NIH HHS / United States |