It had been hoped a single "master" cell could potentially be used to repair all damage in a single organ. Stem cells may be more varied than previously thought. Professor Mario Capecchi, from the University of Utah, found surprising clues that different stem cells might be working together in the same organ. This means experimental treatments relying on the wrong type might fail.Professor Capecchi, writing in the Nature Genetics, said the finding suggested stem cell biology could be "more complicated" than previously thought, which could be bad news for patients hoping for the swift arrival of new therapies.
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 -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.