Bmi1 is expressed in vivo in intestinal stem cells
TLDR
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.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.read more
Citations
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Journal ArticleDOI
Crypt stem cells as the cells-of-origin of intestinal cancer
Nick Barker,Rachel A. Ridgway,Johan H. van Es,Marc van de Wetering,Harry Begthel,Maaike van den Born,Esther Danenberg,Alan Richard Clarke,Owen J. Sansom,Hans Clevers +9 more
TL;DR: It is concluded that stem-cell-specific loss of Apc results in progressively growing neoplasia in long-lived intestinal stem cells.
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Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
Hugo J. Snippert,Laurens G. van der Flier,Toshiro Sato,Johan H. van Es,Maaike van den Born,Carla Kroon-Veenboer,Nick Barker,Allon M. Klein,Jacco van Rheenen,Benjamin D. Simons,Hans Clevers +10 more
TL;DR: Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics, consistent with a model in which the resident stem cells double their numbers each day and stochastically adopt stem or TA fates.
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Cells of origin in cancer
TL;DR: Evidence is also accumulating that cancers of distinct subtypes within an organ may derive from different 'cells of origin', and the identification of these crucial target cell populations may allow earlier detection of malignancies and better prediction of tumour behaviour.
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Coexistence of Quiescent and Active Adult Stem Cells in Mammals
Linheng Li,Hans Clevers +1 more
TL;DR: It is proposed that quiescent and active stem cell populations have separate but cooperative functional roles in a so-called “zoned” stem cell model.
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An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control
TL;DR: The widespread importance of Wnt signaling in driving tissue renewal has been revealed by the identification of Axin2 and Lgr5, genes expressed in cells that are responding to Wnt signals, and this crucial role in stem cell self renewal is reviewed.
References
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Journal ArticleDOI
Identification of stem cells in small intestine and colon by marker gene Lgr5
Nick Barker,Johan H. van Es,Jeroen Kuipers,Pekka Kujala,Maaike van den Born,Miranda Cozijnsen,Andrea Haegebarth,Jeroen Korving,Harry Begthel,Peter J. Peters,Hans Clevers +10 more
TL;DR: The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers, suggesting that it represents the stem cell of the small intestine and colon.
Journal ArticleDOI
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
In-Kyung Park,Dalong Qian,Mark J. Kiel,Michael W. Becker,Michael Pihalja,Irving L. Weissman,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +8 more
TL;DR: The results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs, which are required for haematopoiesis to persist for the lifetime of the animal.
Journal ArticleDOI
Generation of a functional mammary gland from a single stem cell
Mark Shackleton,Mark Shackleton,François Vaillant,François Vaillant,Kaylene J. Simpson,Kaylene J. Simpson,John Stingl,Gordon K. Smyth,Marie Liesse Asselin-Labat,Marie Liesse Asselin-Labat,Li Wu,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Jane E. Visvader,Jane E. Visvader +14 more
TL;DR: It is shown that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo and establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.
Journal ArticleDOI
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells
Julie Lessard,Guy Sauvageau +1 more
TL;DR: Evidence is provided that the proliferative potential of leukaemic stem and progenitor cells lacking Bmi-1 is compromised because they eventually undergo proliferation arrest and show signs of differentiation and apoptosis, leading to transplant failure of the leukaemia.