Colon organoid formation and cryptogenesis are stimulated by growth factors secreted from myofibroblasts
Details
Publication Year 2018, Volume 13, Issue #6, Page e0199412
Journal Title
PLoS One
Publication Type
Journal Article
Abstract
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 (TGFbeta) 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.
Publisher
PLOS
WEHI Research Division(s)
Structural Biology
PubMed ID
29928021
Open Access at Publisher's Site
https://doi.org/10.1371/journal.pone.0199412
NHMRC Grants
NHMRC/1029628 NHMRC/487922
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-02-05 08:28:52
Last Modified: 2019-02-05 08:54:26
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