Gastroenterology

Gastroenterology

Volume 153, Issue 3, September 2017, Pages 674-677.e3
Gastroenterology

Original Research
Brief Report
In Vivo Imaging Reveals Existence of Crypt Fission and Fusion in Adult Mouse Intestine

https://doi.org/10.1053/j.gastro.2017.05.019Get rights and content
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The intestinal epithelium is a repetitive sheet of crypt and villus units with stem cells at the bottom of the crypts. During postnatal development, crypts multiply via fission, generating 2 daughter crypts from 1 parental crypt. In the adult intestine, crypt fission is observed at a low frequency. Using intravital microscopy in Lgr5EGFP-Ires-CreERT2 mice, we monitored individual crypt dynamics over multiple days with single-cell resolution. We discovered the existence of crypt fusion, an almost exact reverse phenomenon of crypt fission, in which 2 crypts fuse into 1 daughter crypt. Examining 819 crypts in 4 mice, we found that 3.5% ± 0.6% of all crypts were in the process of fission, whereas 4.1 ± 0.9% of all crypts were undergoing crypt fusion. As counteracting processes, crypt fission and fusion could regulate crypt numbers during the lifetime of a mouse. Identifying the mechanisms that regulate rates of crypt fission and fusion could provide insights into intestinal adaptation to altered environmental conditions and disease pathogenesis.

Keywords

Development
Renewal
Regeneration
Homeostasis

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Author Contributions J.v.R. and H.J.S. conceived the study and designed the experiments. L.B. and S.I.J.E. performed experiments and analyses. All authors contributed to the writing and have approved the final manuscript. Jacco van Rheenen and Hugo J. Snippert contributed equally to this work.

Conflicts of interest The authors disclose no conflicts.

Funding This work was supported by the Netherlands Organization of Scientific Research NWO (Veni grant 863.15.011 to S.I.J.E), the European Research Council (consolidator grant 648804 to J.v.R.), the Worldwide Cancer Research (grant 13-0297 to J.v.R), and the Dutch Cancer Society KWF (2013-6070 to H.J.S.)

Author names in bold designate shared co-first authorship.

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Authors share co-senior authorship.