scholarly journals Epithelial WNT2B and Desert Hedgehog are necessary for human colonoid regeneration after bacterial cytotoxin injury

2018 ◽  
Author(s):  
Julie G. In ◽  
Jianyi Yin ◽  
Michele Doucet ◽  
Robert N. Cole ◽  
Lauren DeVine ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
E Coli ◽  
Stem Cell Proliferation ◽  
Epithelial Regeneration ◽  
Desert Hedgehog ◽  
Crypt Hyperplasia

SUMMARYIntestinal regeneration and crypt hyperplasia after radiation or pathogen injury relies on Wnt signaling to stimulate stem cell proliferation. Mesenchymal Wnts are essential for homeostasis and regeneration in mice, but the role of epithelial Wnts remains largely uncharacterized. Using the enterohemorrhagicE. colisecreted cytotoxin, EspP to induce injury to human colonoids, we evaluated a simplified, epithelial regeneration model that lacks mesenchymal Wnts. Here, we demonstrate that epithelial-produced WNT2B is upregulated following injury and essential for regeneration. Hedgehog signaling, specifically activation via the ligand Desert Hedgehog (DHH), but not Indian or Sonic Hedgehog, is another driver of regeneration and modulates WNT2B expression. These findings highlight the importance of epithelial WNT2B and DHH in regulating human colonic regeneration after injury.

scholarly journals CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice

2015 ◽  
Vol 309 (11) ◽  
pp. G874-G887 ◽  
Author(s):  
Terrence E. Riehl ◽  
Srikanth Santhanam ◽  
Lynne Foster ◽  
Matthew Ciorba ◽  
William F. Stenson
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Stem Cell ◽  
Hyaluronic Acid ◽  
Postnatal Life ◽  
Epithelial Proliferation ◽  
Stem Cell Proliferation ◽  
Crypt Fission ◽  
Intestinal Length

Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3–8 wk of age to wild-type, CD44−/−, and TLR4−/− mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5+ stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5+ reporter mice from postnatal day 7 to day 14 decreased Lgr5+ cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5+ stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4.

scholarly journals A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development

2017 ◽  
Vol 27 (6) ◽  
pp. 905-913 ◽  
Author(s):  
Kristina Ames ◽  
Dayse S. Da Cunha ◽  
Brenda Gonzalez ◽  
Marina Konta ◽  
Feng Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Germline Development ◽  
Cycle Progression ◽  
Stem Cell Proliferation

scholarly journals Role of the cellular environment in interstitial stem cell proliferation in Hydra

1991 ◽  
Vol 200 (5) ◽  
pp. 269-276 ◽  
Author(s):  
Thomas C. G. Bosch ◽  
Rebecca Rollb�hler ◽  
Birgit Scheider ◽  
Charles N. David
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Stem Cell Proliferation ◽  
Cellular Environment
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