Abstract
BackgroundThe small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Very little is known about human small intestines because mouse fate mapping strategies are impractical in humans. However, it is theoretically possible that stem cell histories are inherently written within their genomes. Genomes appear to record histories (as exemplified by use of molecular clocks), and therefore it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions). Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon.MethodsMethylation patterns in individual crypts from 13 small intestines (17 to 78 years old) were measured by bisulfite sequencing. The methylation patterns were analyzed by a quantitative model to distinguish between immortal or niche stem cell lineages.ResultsAge-related methylation was observed in the human small intestines. Crypt methylation patterns were more consistent with stem cell niches than immortal stem cell lineages. Human large and small intestine crypt niches appeared to have similar stem cell dynamics, but relatively less methylation accumulated with age in the small intestines. There were no apparent stem cell differences between the duodenum and ileum, and stem cell survival did not appear to decline with aging.ConclusionCrypt niches containing multiple stem cells appear to maintain human small intestines. Crypt niches appear similar in the colon and small intestine, and the small intestinal stem cell mitotic rate is the same as or perhaps slower than that of the colon. Although further studies are needed, age-related methylation appears to record somatic cell histories, and a somatic epigenetic molecular clock strategy may potentially be applied to other human tissues to reconstruct otherwise occult stem cell histories.
Highlights
The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells
The schematic of stem cell lineages illustrates that cell division is always asymmetric in immortal stem cell lineages, and predominately asymmetric in a stem cell niche
Crypts of Lieberkühn and villus fragments were isolated from fresh human small intestine (Figure 1) and individual allele methylation patterns were analyzed by bisulfite sequencing
Summary
The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Genomes appear to record histories (as exemplified by use of molecular clocks), and it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions). The small intestine is composed of multiple crypts (of Lieberkühn), which contribute cells to finger-like projections called villi (Figure 1). Stem cell lineages may be immortal if at least one daughter retains stem cell properties after each division. If stem cell lineages were immortal, heterogeneous crypts would not become homogeneous
Sign-in/Register to view highlights & summary 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.
