Abstract
Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance.
Highlights
The inner surface of the colon is lined with simple columnar epithelium structurally organized into crypts
We found that, when various concentrations of ROL were added to the culture, cells treated with 1 μM or 3 μM of ROL formed a somewhat higher number of organoids as compared to those cultured in the absence of ROL (Fig 1A)
As the levels of ROL in human serum were reported to range from 0.5 to 2 μM [25], we presumed that the treatment with physiological concentrations of ROL would have a positive effect on the organoid forming efficiency of cultured colonic epithelial stem cells
Summary
The inner surface of the colon is lined with simple columnar epithelium structurally organized into crypts. The epithelium continues to self-renew throughout the lifetime, fueled by perpetual and rapid cellular turnover of Lgr5+ adult stem cells located near the base of those crypts [1, 2]. The fate determination of those colonic stem cells is, as is the case with small intestinal stem cells, governed by multiple regulatory signals such as the Wnt, bone morphogenic protein (BMP), Notch signaling pathway, and receptor tyrosine kinases [2, 3]. The proliferative activity of colonic stem cells can be reconstituted in vitro by using the organoid culture system that has recently emerged as a powerful tool for studying stem cell. Retinol Promotes Proximal Colon Stem Cell Growth.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
