Bmi1 is expressed in vivo in intestinal stem cells

Abstract

Eugenio Sangiorgi and Mario Capecchi use lineage tracing in mice to identify Bmi1 as a specific marker of a stem cell population located at the +4 position of the small intestinal crypt. Their findings address a long-standing debate in the field and support the existence of two distinct intestinal stem cell populations near the crypt base. Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of β-catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1+ cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis.