Dataset Information

Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.

ABSTRACT:

Background & aims

Intestinal epithelial stem cells that express Lgr5 and/or Bmi1 continuously replicate and generate differentiated cells throughout life¹. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells². However, ablating Paneth cells has no effect on maintenance of functional stem cells^3-5. Here, we demonstrate definitively that a small subset of mesenchymal, subepithelial cells expressing the winged-helix transcription factor Foxl1 are a critical component of the intestinal stem cell niche.

Methods

We genetically ablated Foxl1⁺ mesenchymal cells in adult mice using two separate models by expressing either the human or simian diphtheria toxin receptor (DTR) under Foxl1 promoter control.

Conclusions

Killing Foxl1⁺ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor-cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells.

SUBMITTER: Aoki R

PROVIDER: S-EPMC4772878 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.

Aoki Reina R Shoshkes-Carmel Michal M Gao Nan N Shin Soona S May Catherine L CL Golson Maria L ML Zahm Adam M AM Ray Michael M Wiser Caroline L CL Wright Christopher V E CV Kaestner Klaus H KH

Cellular and molecular gastroenterology and hepatology 20160201 2

<h4>Background & aims</h4>Intestinal epithelial stem cells that express Lgr5 and/or Bmi1 continuously replicate and generate differentiated cells throughout life<sup>1</sup>. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells<sup>2</sup>. However, ablating Paneth cells has no effect on maintenance of functional stem cells<sup>3-5</sup>. Here, we demonstrate definitively that a small subset of mesenchymal, subepithel ...[more]

PMID: 26949732

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Project description:PurposeWe investigated whether human limbal niche cells generate mesenchymal stem cells.MethodsLimbal niche cells were isolated from the limbal stroma by collagenase alone or following dispase removal of the limbal epithelium (D/C), and cultured on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), or coated or three-dimensional Matrigel in embryonic stem cell medium with leukemia inhibitory factor and basic fibroblast growth factor. Expression of cell markers, colony-forming units-fibroblast, tri-lineage differentiation, and ability of supporting limbal epithelial stem/progenitor cells were compared to limbal residual stromal cells.ResultsStromal cells expressing angiogenesis markers were found perivascularly, subjacent to limbal basal epithelial cells, and in D/C and limbal residual stromal cells. When seeded in three-dimensional Matrigel, D/C but not limbal residual stromal cells yielded spheres of angiogenesis progenitors that stabilized vascular networks. Similar to collagenase-isolated cells, D/C cells could be expanded on coated Matrigel for more than 12 passages, yielding spindle cells expressing angiogenesis and mesenchymal stem cells markers, and possessing significantly higher colony-forming units-fibroblast and more efficient tri-lineage differentiation than D/C and limbal residual stromal cells expanded on plastic in DMEM with 10% FBS, of which both lost the pericyte phenotype while limbal residual stromal cells turned into myofibroblasts. Upon reunion with limbal epithelial stem/progenitor cells to form spheres, D/C cells expanded on coated Matrigel maintained higher expression of p63? and lower expression of cytokeratin 12 than those expanded on plastic in DMEM with 10% FBS, while spheres formed with human corneal fibroblasts expressed cytokeratin 12 without p63?.ConclusionsIn the limbal stroma, cells subjacent to limbal basal epithelial cells serve as niche cells, and generate progenitors with angiogenesis and mesenchymal stem cells potentials. They might partake in angiogenesis and regeneration during corneal wound healing.

Dataset Information

Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.

Background & aims

Methods

Conclusions

Publications

Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.

Similar Datasets

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