Quantification of crypt and stem cell evolution in the normal and neoplastic human colon.
Cell Rep
; 8(4): 940-7, 2014 Aug 21.
Article
en En
| MEDLINE
| ID: mdl-25127143
ABSTRACT
Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a "functional" stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC(-/+)). Furthermore, we show that, in adenomatous crypts (APC(-/-)), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30-40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colon
/
Poliposis Adenomatosa del Colon
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido