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Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27 Kip1 and p57 Kip2
Open accessAbstract
The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut‐specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post‐mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin‐dependent kinase (CDK) inhibitors p27 Kip1 and p57 Kip2 . We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild‐type crypt progenitor cells. Thus, our results indicate that Notch‐mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.
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Citations
Cited by
The intestinal crypt, a prototype stem cell compartment
Clevers, H. (2013) · Cell · doi:10.1016/j.cell.2013.07.004 · Cited by 1,223
Self-citationDirect inhibition of the NOTCH transcription factor complex
Moellering, R. E., Cornejo, M., Davis, T. N., Bianco, C. D., Aster, J. C., Blacklow, S. C., Kung, A. L., Gilliland, D. G., Verdine, G. L., & Bradner, J. E. (2009) · Nature · doi:10.1038/nature08543 · Cited by 752
Therapeutic antibody targeting of individual Notch receptors
Wu, Y., Cain-Hom, C., Choy, L., Hagenbeek, T. J., de Leon, G. P., Chen, Y., Finkle, D., Venook, R., Wu, X., Ridgway, J., et al. (2010) · Nature · doi:10.1038/nature08878 · Cited by 720
Paneth Cells: Maestros of the Small Intestinal Crypts
Clevers, H. C., & Bevins, C. L. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183744 · Cited by 699
Self-citationVanDussen, K. L., Carulli, A. J., Keeley, T. M., Patel, S. R., Puthoff, B. J., Magness, S. T., Tran, I. T., Maillard, I., Siebel, C., Kolterud, Å., et al. (2012) · Development · doi:10.1242/dev.070763 · Cited by 578
Metadata
- Authors
- Riccio, O., van Gijn, M. E., Bezdek, A. C., Pellegrinet, L., van Es, J. H., Zimber‐Strobl, U., Strobl, L. J., Honjo, T., Clevers, H., & Radtke, F.
- Venue
- EMBO reports
- Published
- 2008-02-15
- Volume
- 9
- Issue
- 4
- Pages
- 377-383
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- OpenAlex
- W2103750856
- Cited by
- 410
- References
- 0
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27 Kip1 and p57 Kip2. https://app.cochat.ai/papers/10.1038/embor.2008.7
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- Riccio, O., van Gijn, M. E., Bezdek, A. C., Pellegrinet, L., van Es, J. H., Zimber‐Strobl, U., Strobl, L. J., Honjo, T., Clevers, H., & Radtke, F. (2008). Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27 Kip1 and p57 Kip2. EMBO reports. https://doi.org/10.1038/embor.2008.7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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