Colon organoid formation and cryptogenesis are stimulated by growth factors secreted from myofibroblasts.
Hon Yan Kelvin YipChin Wee TanYumiko HirokawaAntony Wilks BurgessPublished in: PloS one (2018)
Although small intestinal epithelial stem cells form crypts when using intestinal culture conditions, colon stem cells usually form colonospheres. Colon mesenchymal cell feeder layers can stimulate colon crypts to form organoids and produce crypts. We have investigated whether conditioned medium from colon mesenchymal cells can also stimulate colonosphere and organoid cryptogenesis. We prepared conditioned medium (CM) from WEHI-YH2 cells (mouse colon myofibroblasts); the CM stimulated both colonosphere formation and organoid cryptogenesis in vitro. The colon organoid-stimulating factors in WEHI-YH2 CM are inactivated by heating and trypsin digestion and proteins can be concentrated by ultrafiltration. Both the colonosphere- and organoid cryptogenesis- stimulatory effects of the CM are independent of canonical Wnt and Notch signaling. In contrast, bone morphogenetic protein 4 (BMP4) abolishes colonosphere formation and organoid cryptogenesis. The Transforming Growth Factor beta (TGFβ) Type I receptor kinase inhibitor (A83-01) stimulates colonosphere formation, whereas the Epidermal Growth Factor receptor (EGFR) kinase inhibitor (AG1478) reduces the formation of colonospheres, but in the presence of EGF, a "just-right" concentration of AG1478 increases colon organoid cryptogenesis.
Keyphrases
- stem cells
- epidermal growth factor receptor
- transforming growth factor
- induced apoptosis
- small cell lung cancer
- tyrosine kinase
- epithelial mesenchymal transition
- cell therapy
- magnetic resonance
- bone marrow
- cell proliferation
- cell cycle arrest
- magnetic resonance imaging
- computed tomography
- mesenchymal stem cells
- quantum dots
- cell death
- mass spectrometry
- atomic force microscopy
- single molecule
- high speed
- solar cells