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Your search keyword '"Bruens, L"' showing total 4 results
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4 results on '"Bruens, L"'

1. Wnt ligands influence tumour initiation by controlling the number of\ud intestinal stem cells

Author

Huels, D.J., Bruens, L., Hodder, M.C., Cammareri, P., Campbell, A.D., Ridgway, R.A., Gay, D.M., Solar Abboud, M., Faller, W.J., Nixon, C., Zeiger, L.B., McLaughlin, M.E., Morrissey, E., Winton, D.J., Snippert, H.J., van Rheenen, J., and Sansom, O.J.

Abstract

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called\ud 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against\ud the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt\ud secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+\ud stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that\ud crypts become rapidly derived from a single stem cell. Stem cells located further from the\ud base are lost and the pool of competing stem cells is reduced. We tested whether this loss of\ud stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion\ud accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis.\ud Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation\ud speed of Apc mutations and the speed and likelihood of adenoma formation.

Published
2018

2. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells

Author

Huels, D. J., Bruens, L., Hodder, M. C., Cammareri, P., Campbell, A. D., Ridgway, R. A., Gay, D. M., Solar-Abboud, M., Faller, W. J., Nixon, C., Zeiger, L. B., McLaughlin, M. E., Morrissey, E., Winton, D. J., Snippert, H. J., Van Rheenen, J., Sansom, O. J., Huels, D. J., Bruens, L., Hodder, M. C., Cammareri, P., Campbell, A. D., Ridgway, R. A., Gay, D. M., Solar-Abboud, M., Faller, W. J., Nixon, C., Zeiger, L. B., McLaughlin, M. E., Morrissey, E., Winton, D. J., Snippert, H. J., Van Rheenen, J., and Sansom, O. J.

Published
2018

3. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells

Author

CMM, CMM Groep Snippert, Cancer, CMM Sectie Molecular Cancer Research, Huels, D. J., Bruens, L., Hodder, M. C., Cammareri, P., Campbell, A. D., Ridgway, R. A., Gay, D. M., Solar-Abboud, M., Faller, W. J., Nixon, C., Zeiger, L. B., McLaughlin, M. E., Morrissey, E., Winton, D. J., Snippert, H. J., Van Rheenen, J., Sansom, O. J., CMM, CMM Groep Snippert, Cancer, CMM Sectie Molecular Cancer Research, Huels, D. J., Bruens, L., Hodder, M. C., Cammareri, P., Campbell, A. D., Ridgway, R. A., Gay, D. M., Solar-Abboud, M., Faller, W. J., Nixon, C., Zeiger, L. B., McLaughlin, M. E., Morrissey, E., Winton, D. J., Snippert, H. J., Van Rheenen, J., and Sansom, O. J.

Published
2018

4. Retrograde movements determine effective stem cell numbers in the intestine.

Author

Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P, Simons BD, Katajisto P, Hannezo E, and van Rheenen J

Subjects
Animals, Intestinal Mucosa cytology, Intestine, Small cytology, Mice, Receptors, G-Protein-Coupled, Wnt Proteins, Cell Count, Cell Movement, Intestines cytology, Stem Cells cytology
Abstract

The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts 1-3 . Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2022
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