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.
Highlights
Vitamin A, a small dietary component of 286 Da size, discovered almost 100 years ago [1,2], is essential for vertebrate embryogenesis, normal growth and development [3,4,5,6] and its deficiency leads to reproductive failure in females [7]
The cells deprived of vitamin A/retinol defaulted to basal levels of ATP synthesis which resulted in acute energy crisis
Vitamin A/retinol is absorbed from food in the small intestine
Summary
Vitamin A, a small dietary component of 286 Da size, discovered almost 100 years ago [1,2], is essential for vertebrate embryogenesis, normal growth and development [3,4,5,6] and its deficiency leads to reproductive failure in females [7]. In addition to its role in cell differentiation via retinoic acid, recent studies have demonstrated that vitamin A/retinol has a direct function in the maintenance of self-renewal and prevention of differentiation of pluripotent stem cells [12,13,14,15]. The cells retain the capacity to differentiate into cardiomyocytes, neuronal cells and visceral endoderm, the derivatives of all three germ layers Their studies revealed that retinoic acid prevented the differentiation of ESCs by up regulating the expression of LIF, Wnt3a, Wnt5a, and Wnt. The pluripotency of mGSCs was further proven by teratoma formation after implantation into immunodeficient mice which contained derivatives of endodermal, mesodermal, and ectodermal embryonic germ layers including stratified cell epithelium, neuronal cells, cartilage, muscle, glandular structures, and endodermal high prismatic epithelium [15]
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