Journal article

Paneth Cell-Rich Regions Separated by a Cluster of Lgr5 Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche

Alistair J Langlands, Axel A Almet, Paul L Appleton, Ian P Newton, James M Osborne, Inke S Nathke

PLOS BIOLOGY | PUBLIC LIBRARY SCIENCE | Published : 2016

Abstract

The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal orga..

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University of Melbourne Researchers

Grants

Awarded by Cancer Research UK


Awarded by Wellcome Trust


Awarded by ARC


Awarded by Engineering and Physical Sciences Research Council


Awarded by Medical Research Council


Funding Acknowledgements

Funding was provided by program grant C430/A11243 from Cancer Research UK (http://www.cancerresearchuk.org/) to ISN supporting AJL, IPN, and PLA. Tissue imaging was also supported by a multiuser equipment grant from the Wellcome Trust (http://www.wellcome.ac.uk/) (WT101468). AAA was partially supported by an ARC (http://www.arc.gov.au/) Discovery Project grant (DP110100795). JMO is supported by the University of Melbourne School of Mathematics and Statistics (http://www.ms.unimelb.edu.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank Prof. Laura Machesky (Beatson Institute) for providing tissue from Life-Act-GFP intestinal organoids. We are grateful for support from the Dundee Light Microscopy facility. We also thank Prof. Barry Hughes and Prof. Kerry Landman for valuable contributions to the mathematical modelling aspect of this work.