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Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells
Open accessAbstract
Notch signaling is known to regulate the proliferation and differentiation of intestinal stem and progenitor cells; however, direct cellular targets and specific functions of Notch signals had not been identified. We show here in mice that Notch directly targets the crypt base columnar (CBC) cell to maintain stem cell activity. Notch inhibition induced rapid CBC cell loss, with reduced proliferation, apoptotic cell death and reduced efficiency of organoid initiation. Furthermore, expression of the CBC stem cell-specific marker Olfm4 was directly dependent on Notch signaling, with transcription activated through RBP-Jκ binding sites in the promoter. Notch inhibition also led to precocious differentiation of epithelial progenitors into secretory cell types, including large numbers of cells that expressed both Paneth and goblet cell markers. Analysis of Notch function in Atoh1-deficient intestine demonstrated that the cellular changes were dependent on Atoh1, whereas Notch regulation of Olfm4 gene expression was Atoh1 independent. Our findings suggest that Notch targets distinct progenitor cell populations to maintain adult intestinal stem cells and to regulate cell fate choice to control epithelial cell homeostasis.
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Cites
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Cheng, H., & Leblond, C. P. (1974) · American Journal of Anatomy · doi:10.1002/aja.1001410407 · Cited by 1,735
van Es, J. H., van Gijn, M. E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., Cozijnsen, M., Robine, S., Winton, D. J., Radtke, F., et al. (2005) · Nature · doi:10.1038/nature03659 · Cited by 1,543
Control of endodermal endocrine development by Hes-1
Jensen, J., Pedersen, E. E., Galante, P., Hald, J., Heller, R. S., Ishibashi, M., Kageyama, R., Guillemot, F., Serup, P., & Madsen, O. D. (2000) · Nature Genetics · doi:10.1038/71657 · Cited by 1,155
Canonical Wnt signals are essential for homeostasis of the intestinal epithelium
Pinto, D., Gregorieff, A., Begthel, H., & Clevers, H. (2003) · Genes & Development · doi:10.1101/gad.267103 · Cited by 1,026
Notch signals control the fate of immature progenitor cells in the intestine
Fre, S., Huyghe, M., Mourikis, P., Robine, S., Louvard, D., & Artavanis-Tsakonas, S. (2005) · Nature · doi:10.1038/nature03589 · Cited by 935
Requirement of Math1 for Secretory Cell Lineage Commitment in the Mouse Intestine
Yang, Q., Bermingham, N. A., Finegold, M. J., & Zoghbi, H. Y. (2001) · Science · doi:10.1126/science.1065718 · Cited by 919
Notch signaling controls multiple steps of pancreatic differentiation
Murtaugh, L. C., Stanger, B. Z., Kwan, K. M., & Melton, D. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436557100 · Cited by 782
Transcription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate
van der Flier, L. G., van Gijn, M. E., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D. E., Begthel, H., van den Born, M., Guryev, V., Oving, I., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.031 · Cited by 724
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
Self-citationWong, G. T., Manfra, D., Poulet, F. M., Zhang, Q., Josien, H., Bara, T., Engstrom, L., Pinzon-Ortiz, M., Fine, J. S., Lee, H.-J. J., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311652200 · Cited by 718
Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
Zhu, L., Gibson, P., Currle, D. S., Tong, Y., Richardson, R. J., Bayazitov, I. T., Poppleton, H., Zakharenko, S., Ellison, D. W., & Gilbertson, R. J. (2009) · Nature · doi:10.1038/nature07589 · Cited by 668
Cheng, H. (1974) · American Journal of Anatomy · doi:10.1002/aja.1001410404 · Cited by 617
Cheng, H., & Leblond, C. P. (1974) · American Journal of Anatomy · doi:10.1002/aja.1001410403 · Cited by 592
Milano, J., McKay, J., Dagenais, C., Foster-Brown, L., Pognan, F., Gadient, R., Jacobs, R. T., Zacco, A., Greenberg, B., & Ciaccio, P. J. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh254 · Cited by 576
Bastide, P., Darido, C., Pannequin, J., Kist, R., Robine, S., Marty-Double, C., Bibeau, F., Scherer, G., Joubert, D., Hollande, F., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704152 · Cited by 494
Jenny, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf649 · Cited by 492
Targeting Notch to Target Cancer Stem Cells
Pannuti, A., Foreman, K., Rizzo, P., Osipo, C., Golde, T., Osborne, B., & Miele, L. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2823 · Cited by 450
Dll1- and Dll4-Mediated Notch Signaling Are Required for Homeostasis of Intestinal Stem Cells
Pellegrinet, L., Rodilla, V., Liu, Z., Chen, S., Koch, U., Espinosa, L., Kaestner, K. H., Kopan, R., Lewis, J., & Radtke, F. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.005 · Cited by 431
Gerbe, F., van Es, J. H., Makrini, L., Brulin, B., Mellitzer, G., Robine, S., Romagnolo, B., Shroyer, N. F., Bourgaux, J.-F., Pignodel, C., et al. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201010127 · Cited by 430
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) · EMBO reports · doi:10.1038/embor.2008.7 · Cited by 410
SOX9 Is Required for the Differentiation of Paneth Cells in the Intestinal Epithelium
Mori–Akiyama, Y., van den Born, M., van Es, J. H., Hamilton, S. R., Adams, H. P., Zhang, J., Clevers, H., & de Crombrugghe, B. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.05.020 · Cited by 343
Shroyer, N. F., Wallis, D., Venken, K. J. T., Bellen, H. J., & Zoghbi, H. Y. (2005) · Genes & Development · doi:10.1101/gad.1353905 · Cited by 310
Intestine-Specific Ablation of Mouse atonal homolog 1 (Math1) Reveals a Role in Cellular Homeostasis
Shroyer, N. F., Helmrath, M. A., Wang, V. Y. –., Antalffy, B., Henning, S. J., & Zoghbi, H. Y. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.047 · Cited by 309
Direct regulation of intestinal fate by Notch
Stanger, B. Z., Datar, R., Murtaugh, L. C., & Melton, D. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505690102 · Cited by 294
Mastermind critically regulates Notch-mediated lymphoid cell fate decisions
Maillard, I., Weng, A. P., Carpenter, A. C., Rodriguez, C. G., Sai, H., Xu, L., Allman, D., Aster, J. C., & Pear, W. S. (2004) · Blood · doi:10.1182/blood-2004-02-0514 · Cited by 284
Self-citationRecognition sequence of a highly conserved DNA binding protein RBP-Jx
Tun, T., Hamaguchi, Y., Matsunami, N., Furukawa, T., Honjo, T., & Kawaichi, M. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.6.965 · Cited by 281
Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice
Garabedian, E. M., Roberts, L. J. J., McNevin, M. S., & Gordon, J. I. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23729 · Cited by 277
Gregorieff, A., Stange, D. E., Kujala, P., Begthel, H., van den Born, M., Korving, J., Peters, P. J., & Clevers, H. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.044 · Cited by 263
Delta-Notch signalling controls commitment to a secretory fate in the zebrafish intestine
Crosnier, C., Vargesson, N., Gschmeissner, S., Ariza-McNaughton, L., Morrison, A., & Lewis, J. (2005) · Development · doi:10.1242/dev.01644 · Cited by 262
Patel, S. R., Kim, D., Levitan, I., & Dressler, G. R. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.09.004 · Cited by 249
Self-citationProminin-1/CD133 Marks Stem Cells and Early Progenitors in Mouse Small Intestine
Snippert, H. J., van Es, J. H., van den Born, M., Begthel, H., Stange, D. E., Barker, N., & Clevers, H. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.03.002 · Cited by 217
Target Selectivity of Vertebrate Notch Proteins
Ong, C.-T., Cheng, H.-T., Chang, L.-W., Ohtsuka, T., Kageyama, R., Stormo, G. D., & Kopan, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m506108200 · Cited by 216
Noah, T. K., Kazanjian, A., Whitsett, J., & Shroyer, N. F. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.09.020 · Cited by 202
Cheng, H. (1974) · American Journal of Anatomy · doi:10.1002/aja.1001410406 · Cited by 174
Expression of Notch pathway components in fetal and adult mouse small intestine
Schröder, N., & Gossler, A. (2002) · Gene Expression Patterns · doi:10.1016/s1567-133x(02)00060-1 · Cited by 164
Tomarev, S. I., & Nakaya, N. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8076-x · Cited by 162
Gracz, A. D., Ramalingam, S., & Magness, S. T. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00470.2009 · Cited by 160
Self-citationVanDussen, K. L., & Samuelson, L. C. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.07.026 · Cited by 149
Self-citationIntestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors
van Es, J. H., Geest, N. D., van den Born, M., Clevers, H. C., & Hassan, B. A. (2010) · Nature Communications · doi:10.1038/ncomms1017 · Cited by 145
Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
Vooijs, M., Ong, C., Hadland, B., Huppert, S. S., Liu, Z., Korving, J., van den Born, M., Stappenbeck, T. S., Wu, Y., Clevers, H. C., et al. (2007) · Development · doi:10.1242/dev.02733 · Cited by 144
Zhang, J., Liu, W.-L., Tang, D. C., Chen, L., Wang, M., Pack, S., Zhuang, Z., & Rodgers, G. P. (2002) · Gene · doi:10.1016/s0378-1119(01)00763-6 · Cited by 143
Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection
Liu, W., Yan, M., Liu, Y., Wang, R., Li, C., Deng, C., Singh, A., Coleman, W. G., & Rodgers, G. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001269107 · Cited by 143
PANETH AND GOBLET CELL RENEWAL IN MOUSE DUODENAL CRYPTS
Troughton, W. D., & Trier, J. S. (1969) · The Journal of Cell Biology · doi:10.1083/jcb.41.1.251 · Cited by 141
GW112, A Novel Antiapoptotic Protein That Promotes Tumor Growth
Zhang, X., Huang, Q., Yang, Z., Li, Y., & Li, C. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3443 · Cited by 138
Pinto, D., Robine, S., Jaisser, F., Marjou, F. E., & Louvard, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6476 · Cited by 134
Gastric tuft cells express DCLK1 and are expanded in hyperplasia
Saqui–Salces, M., Keeley, T. M., Grosse, A. S., Qiao, X. T., Zaatari, M. E., Gumucio, D. L., Samuelson, L. C., & Merchant, J. L. (2011) · Histochemistry and Cell Biology · doi:10.1007/s00418-011-0831-1 · Cited by 120
Self-citationArnett, K. L., Hass, M. R., McArthur, D. G., Ilagan, M. X. G., Aster, J. C., Kopan, R., & Blacklow, S. C. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1938 · Cited by 116
Structure and function of γ-secretase
Tolia, A., & Strooper, B. D. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.10.007 · Cited by 101
The glycoprotein hGC-1 binds to cadherin and lectins
Liu, W., Chen, L., Zhu, J., & Rodgers, G. P. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.02.011 · Cited by 99
Expression of Dll4 during mouse embryogenesis suggests multiple developmental roles
Benedito, R., & Duarte, A. (2005) · Gene Expression Patterns · doi:10.1016/j.modgep.2005.04.004 · Cited by 98
Kim, T., & Shivdasani, R. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.188797 · Cited by 96
Neurogenin 3 and the enteroendocrine cell lineage in the adult mouse small intestinal epithelium
Bjerknes, M., & Cheng, H. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.07.040 · Cited by 96
Kazanjian, A. A., Noah, T. K., Brown, D., Burkart, J. T., & Shroyer, N. F. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.05.081 · Cited by 92
Olfactomedin 4 promotes S‐phase transition in proliferation of pancreatic cancer cells
Kobayashi, D., Koshida, S., Moriai, R., Tsuji, N., & Watanabe, N. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00397.x · Cited by 90
Takashima, S., Adams, K. L., Ortiz, P. A., Ying, C. T., Moridzadeh, R. S., Younossi‐Hartenstein, A., & Hartenstein, V. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.01.039 · Cited by 79
Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium
Bjerknes, M., & Cheng, H. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.06.021 · Cited by 79
Keeley, T. M., & Samuelson, L. C. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00239.2010 · Cited by 60
Self-citationThe regulation of OLFM4 expression in myeloid precursor cells relies on NF‐κB transcription factor
Chin, K., Aerbajinai, W., Zhu, J., Drew, L. R., Chen, L., Liu, W., & Rodgers, G. P. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07368.x · Cited by 51
Fingleton, B., Powell, W. C., Crawford, H. C., Couchman, J., & Matrisian, L. M. (2007) · Hybridoma · doi:10.1089/hyb.2006.028 · Cited by 24
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Martini, E., Krug, S. M., Siegmund, B., Neurath, M. F., & Becker, C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.03.007 · Cited by 668
Wang, Y., Gunasekara, D. B., Reed, M. I., DiSalvo, M., Bultman, S. J., Sims, C. E., Magness, S. T., & Allbritton, N. L. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.03.005 · Cited by 373
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Metadata
- Authors
- VanDussen, 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., Grosse, A. S., Gumucio, D. L., Ernst, S. A., Tsai, Y.-H., Dempsey, P. J., & Samuelson, L. C.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2012-02-01
- Volume
- 139
- Issue
- 3
- Pages
- 488-497
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2111214065
- Cited by
- 578
- References
- 62
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- green
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