Cancer Institute A national cancer institute
designated cancer center

Calvin Kuo

Publication Details

  • The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Yan, K. S., Chia, L. A., Li, X., Ootani, A., Su, J., Lee, J. Y., Su, N., Luo, Y., Heilshorn, S. C., Amieva, M. R., Sangiorgi, E., Capecchi, M. R., Kuo, C. J. 2012; 109 (2): 466-471

    Abstract:

    The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1(+) ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1(+) ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5(+) ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration.

    View details for DOI 10.1073/pnas.1118857109

    View details for Web of Science ID 000298950200030

    View details for PubMedID 22190486

Stanford Medicine Resources:

Footer Links: