Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Mar 21;6(3):1209-22.
doi: 10.3390/nu6031209.

Vitamin A/retinol and maintenance of pluripotency of stem cells

Jaspal S Khillan  1
Affiliations
Review

Vitamin A/retinol and maintenance of pluripotency of stem cells

Jaspal S Khillan. Nutrients. .

Abstract

Retinol, the alcohol form of vitamin A is a key dietary component that plays a critical role in vertebrate development, cell differentiation, reproduction, vision and immune system. Natural and synthetic analogs of retinol, called retinoids, have generally been associated with the cell differentiation via retinoic acid which is the most potent metabolite of retinol. However, a direct function of retinol has not been fully investigated. New evidence has now emerged that retinol supports the self-renewal of stem cells including embryonic stem cells (ESCs), germ line stem cells (GSCs) and cancer stem cells (CSCs) by activating the endogenous machinery for self-renewal by a retinoic acid independent mechanism. The studies have also revealed that stem cells do not contain enzymes that are responsible for metabolizing retinol into retinoic acid. This new function of retinol may have important implications for stem cell biology which can be exploited for quantitative production of pure population of pluripotent stem cells for regenerative medicine as well as clinical applications for cancer therapeutics.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Model for retinol metabolism in a target cell: vitamin A/retinol (Rol) binds with the transthyretin (TTR) and retinol binding protein (RBP) to form a ternary complex that binds to STRA6 receptor on the surface of the target cell. Inside the cytoplasm, retinol binds to cellular retinol binding protein (CRBP) and is oxidized to retinaldehyde (RAL) by alcohol dehydrogenase (ADH4). RAL is then converted into retinoic acid (RA) by retinaldehyde dehydrogenases (RALDH). Retinoic acid isthen transported into the nucleus by binding to the cellular retinoic acid binding receptor (CRABP) where it forms a complex with RAR and RXR receptors that binds with retinoic acid response elements (RARE) in the promoter region of responsive genes to activate their expression.
Figure 2
Figure 2
Model for retinol metabolism in ESCs: Vitamin A/retinol (Rol) activates PI3 kinase in ESCs by engaging IGF1R via yet to be determined mechanism that leads to the activation of Akt/PKB via phosphorylation at serine308 and serine473 which then activates downstream targets mTORCI and mTORC2 complexes which ultimately results in the activation of pluripotent stem cell specific gene NANOG and OCT4.
See this image and copyright information in PMC

References

    1. McCollum E.V., Davis M. The necessity of certain lipins in the diet during growth. J. Biol. Chem. 1913;15:167–175. - PubMed
    1. Osborne T.B., Mendel L.B. The relation of growth to the chemical constituents of the diet. J. Biol. Chem. 1913;145:311–326.
    1. McCaffery P., Dräger U.C. Regulation of retinoic acid signaling in the embryonic nervous system: A master differentiation factor. Cytokine Growth Factor Rev. 2000;11:233–249. doi: 10.1016/S1359-6101(00)00002-2. - DOI - PubMed
    1. Zile M.H. Function of vitamin A in vertebrate development. J. Nutr. 2001;131:705–708. - PubMed
    1. Clagett-Dame M., DeLuca H.F. The role of vitamin a in mammalian reproduction and embryonic development. Annu. Rev. Nutr. 2000;22:347–381. doi: 10.1146/annurev.nutr.22.010402.102745E. - DOI - PubMed

MeSH terms