Dysfunction of the limbal epithelial stem cell niche in aniridia-associated keratopathy

2021 ◽  
Author(s):  
Ursula Schlötzer-Schrehardt ◽  
Lorenz Latta ◽  
Andreas Gießl ◽  
Matthias Zenkel ◽  
Fabian N. Fries ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Epithelial Stem Cell ◽  
Cell Niche

MESENCHYMAL TNFR1 EXPRESSION PRESERVES THE COLONIC EPITHELIAL STEM CELL NICHE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Safina Gadeock ◽  
Cambrian Liu ◽  
Brent Polk
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Mesenchymal Cells ◽  
Epithelial Stem Cells ◽  
Epithelial Stem Cell ◽  
Long Term Treatment ◽  
Lgr5 Expression ◽  
Cell Niche

Abstract Tumor necrosis factor (TNF) is a highly expressed cytokine in inflammatory bowel disease (IBD). Although TNF can induce colonic epithelial dysfunction and apoptosis, recent studies suggest that TNF signalling promotes epithelial wound repair and stem cell function. Here we investigated the role of TNF receptor 1 (TNFR1) in mediating TNF’s effects on colonic epithelial stem cells, integral to mucosal healing in colitis. We demonstrate that Tnfr1-/- mice exhibit loss in Lgr5 expression (-52%, p<0.02; N=6) compared to wildtype (WT) controls. However, the opposite result was found in vitro, wherein murine Tnfr1-/- colonoids demonstrated a significant increase in Lgr5 expression (66%, p<0.007; N=6) compared to WT colonoids. Similarly, human colonoids treated with an anti-TNFR1 antibody also demonstrated an increase in Lgr5 expression, relative to IgG controls. To resolve the contradiction in the in vivo versus in vitro environment, we hypothesized that mesenchymal TNFR1 expression regulates the epithelial stem cell niche. To determine the relationships between these cell types, we co-cultured WT or Tnfr1-/- colonoids with WT or Tnfr1-/- colonic myofibroblasts (CMFs). We found that epithelial Lgr5 expression was significantly higher (by 52%, p<0.05; N=3) when co-cultured with WT compared to TNFR1-/- myofibroblasts. The loss of TNFR1 expression in vivo increases the number of αSMA+ mesenchymal cells by nearly 56% (N=6) but considerably reduces the pericryptal PDGFRα+ cells, suggesting modifications in mesenchymal populations that contribute to the epithelial stem cell niche. Functionally, primary Tnfr1-/--CMFs displayed PI3k (p<0.001; N=3) and MAPK (p<0.01; N=3)-dependent increases in migration, proliferation, and differentiation, but RNA profiling demonstrated by diminished levels of stem cell niche factors, Rspo3 (-80%, p<0.0001; N=6) and Wnt2b (-63%, p<0.008; N=6) compared to WT-CMFs. Supplementation with 50ng recombinant Rspo3 for 5 d to Lgr5-GFP organoids co-cultured with TNFR1-/--CMFs restored Lgr5 expression to wildtype levels. Therefore, TNFR1-mediated TNF signalling in mesenchymal cells promotes their ability to support an epithelial stem cell niche. These results should motivate future studies of the stem cell niche in the context of long-term treatment with anti-TNF therapies.

800 MESENCHYMAL TNFR1 EXPRESSION PRESERVES THE COLONIC EPITHELIAL STEM CELL NICHE

2021 ◽  
Vol 160 (6) ◽  
pp. S-165
Author(s):  
Safina Gadeock ◽  
Cambrian Y. Liu ◽  
D. Brent Polk
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Epithelial Stem Cell ◽  
Cell Niche

Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche

2013 ◽  
Vol 231 (2) ◽  
pp. 236-247 ◽  
Author(s):  
Matthew J Harries ◽  
Katja Meyer ◽  
Iskander Chaudhry ◽  
Jennifer E Kloepper ◽  
Enrique Poblet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Immune Privilege ◽  
Lichen Planopilaris ◽  
Epithelial Stem Cell ◽  
Cell Niche

scholarly journals Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury

2011 ◽  
Vol 121 (11) ◽  
pp. 4409-4419 ◽  
Author(s):  
Thomas Volckaert ◽  
Erik Dill ◽  
Alice Campbell ◽  
Caterina Tiozzo ◽  
Susan Majka ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Mouse Lung ◽  
Airway Epithelial ◽  
Epithelial Stem Cell ◽  
Cell Niche

scholarly journals Advanced Imaging and Tissue Engineering of the Human Limbal Epithelial Stem Cell Niche

2014 ◽  
pp. 179-202 ◽  
Author(s):  
Isobel Massie ◽  
Marc Dziasko ◽  
Alvena Kureshi ◽  
Hannah J. Levis ◽  
Louise Morgan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Advanced Imaging ◽  
Epithelial Stem Cell ◽  
Cell Niche
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