Abstract
Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.
Highlights
Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while acting as a critical barrier to the outside world
Crypts are created by invagination of the epithelium into the underlying stroma in a process that begins during late organogenesis and is completed postnatally in mice, whereas, in humans, it is completed several weeks prior to birth [1]
Seeding of organoids from freshly isolated crypts or single intestinal stem cells (ISCs) activates Yap-dependent fetal genes. This was comprehensively demonstrated by Liberali and colleagues, who visualized in real time and transcriptionally profiled developing organoids derived from single Lgr5+ ISCs [64]
Summary
Several robust injury models based on gamma irradiation or chemical insults have been developed to study regenerative responses in the gut. Replenishment of lost ISCs and repair of damaged crypts appear to depend on the temporary reversion of the adult gut epithelium into an embryonic state Note that this process may be restricted to murine intestinal regeneration, as the fetal program is enriched in biopsy material from ulcerative colitis patients [50]. Numerous studies tracking the fate of tuft cells, Paneth cells, Goblet cells, and enterocytes have shown that lineage committed cells are capable of dedifferentiating into multipotent ISCs during gut regeneration [57] Together, these results suggest a model whereby lineage-restricted progenitors dedifferentiate into a fetal-like state in response to tissue damage and Yap induction. Ascl2+ cells, which acquire revSCs are the earliest dedifferentiating celland type that may give rise to Hopx progressivelysignaling, more homeostatic features During this process, fetal homeostatic stem-cell genes would mark+ early and which acquire progressively more homeostatic features.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
