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The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology

Overview of attention for article published in Biological Research, January 2018
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  • High Attention Score compared to outputs of the same age and source (80th percentile)

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Title
The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology
Published in
Biological Research, January 2018
DOI 10.1186/s40659-017-0151-6
Pubmed ID
Authors

Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sørlie

Abstract

The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells. The LGR5+ stem cells are located in the crypt base and capable of regenerating all intestinal epithelial cell lineages. We treated Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice with the tankyrase inhibitor G007-LK for up to 3 weeks to assess the effect on duodenal stem cell homeostasis and on the integrity of intestinal epithelium. At the administered doses, G007-LK treatment inhibited WNT signalling in LGR5+ stem cells and reduced the number and distribution of cells traced from duodenal LGR5+ stem cells. However, the gross morphology of the duodenum remained unaltered and G007-LK-treated mice showed no signs of weight loss or any other visible morphological changes. The inhibitory effect on LGR5+ stem cell proliferation was reversible. We show that the tankyrase inhibitor G007-LK is well tolerated by the mice, although proliferation of the LGR5+ intestinal stem cells was inhibited. Our observations suggest the presence of a tankyrase inhibitor-resistant cell population in the duodenum, able to rescue tissue integrity in the presence of G007-LK-mediated inhibition of the WNT signalling dependent LGR5+ intestinal epithelial stem cells.

X Demographics

X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Student > Bachelor 5 16%
Student > Master 4 13%
Researcher 4 13%
Professor 1 3%
Other 1 3%
Unknown 11 34%
Readers by discipline Count As %
Medicine and Dentistry 6 19%
Agricultural and Biological Sciences 5 16%
Biochemistry, Genetics and Molecular Biology 4 13%
Pharmacology, Toxicology and Pharmaceutical Science 3 9%
Immunology and Microbiology 1 3%
Other 2 6%
Unknown 11 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 January 2018.
All research outputs
#7,899,670
of 25,382,440 outputs
Outputs from Biological Research
#88
of 642 outputs
Outputs of similar age
#147,899
of 450,867 outputs
Outputs of similar age from Biological Research
#2
of 10 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 642 research outputs from this source. They receive a mean Attention Score of 3.3. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 450,867 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 8 of them.