Crypt fusion as a homeostatic mechanism in the human colon.
Date
2019-11-01Author
Baker, A-M
Gabbutt, C
Williams, MJ
Cereser, B
Jawad, N
Rodriguez-Justo, M
Jansen, M
Barnes, CP
Simons, BD
McDonald, SA
Graham, TA
Wright, NA
Type
Journal Article
Metadata
Show full item recordAbstract
OBJECTIVE: The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove crypts, as recently shown in mouse models, is uncertain. We examined whether crypt fusion (the process of two neighbouring crypts fusing into a single daughter crypt) occurs in the human colon. DESIGN: We used somatic alterations in the gene cytochrome c oxidase (CCO) as lineage tracing markers to assess the clonality of bifurcating colon crypts (n=309 bifurcating crypts from 13 patients). Mathematical modelling was used to determine whether the existence of crypt fusion can explain the experimental data, and how the process of fusion influences the rate of crypt fission. RESULTS: In 55% (21/38) of bifurcating crypts in which clonality could be assessed, we observed perfect segregation of clonal lineages to the respective crypt arms. Mathematical modelling showed that this frequency of perfect segregation could not be explained by fission alone (p<10-20). With the rates of fission and fusion taken to be approximately equal, we then used the distribution of CCO-deficient patch size to estimate the rate of crypt fission, finding a value of around 0.011 divisions/crypt/year. CONCLUSIONS: We have provided the evidence that human colonic crypts undergo fusion, a potential homeostatic process to regulate total crypt number. The existence of crypt fusion in the human colon adds a new facet to our understanding of the highly dynamic and plastic phenotype of the colonic epithelium.
Collections
Subject
colon crypt
crypt fission
crypt fusion
evolutionary dynamics
lineage tracing
mathematical modelling
Aberrant Crypt Foci
Adult
Aged
Cell Culture Techniques
Cell Fusion
Colon
Electron Transport Complex IV
Female
Homeostasis
Humans
Intestinal Mucosa
Male
Middle Aged
Models, Theoretical
Research team
Genomics & evolut dynam
Language
eng
Date accepted
2019-02-22
License start date
2019-11-01
Citation
Gut, 2019, 68 (11), pp. 1986 - 1993
Publisher
BMJ PUBLISHING GROUP