Retinoid supplementation of differentiating human neural progenitors and embryonic stem cells leads to enhanced neurogenesis in vitro.
Summary of "Retinoid supplementation of differentiating human neural progenitors and embryonic stem cells leads to enhanced neurogenesis in vitro."
Retinoids are important molecules involved in the development and homeostasis of the nervous system. As such, various retinoid derivatives are often found in culture media and supplement formulations to support the growth and maintenance of neural cells. However, all-trans-retinoic acid (ATRA) and its associated derivatives are light sensitive and are highly susceptible to isomerisation. This can lead to variability in retinoid concentrations and the nature of the retinoid species present in culture solutions which in turn can influence biological activity and introduce inconsistency. We have previously described the development of the synthetic retinoid derivative, EC23, as a chemically and light stable alternative that does not degrade and has biological activity similar to ATRA. In this study we demonstrate that the addition of exogenous retinoid can significantly enhance neuronal differentiation of both human neuroprogenitor and human embryonic stem cells. In the former, both ATRA and EC23 induced increased maturation and stabilisation of the axonal cytoskeleton. However, EC23 was particularly potent at lower nanomolar concentrations resulting in significantly greater neurogenesis than ATRA. In ES cells enhanced motor neuron marker expression was also detected in response to both retinoids when incorporated into an established protocol for neuronal differentiation. We propose that synthetic retinoid EC23 represents a valuable addition to the formulation of new and existing culture supplements to enhance neuronal differentiation whilst enabling improved consistency.
Affiliation
School of Biological and Biomedical Sciences, Durham University, Science Laboratories, South Road, Durham, UK.
Journal Details
This article was published in the following journal.
Name: Journal of neuroscience methods
ISSN: 1872-678X
Pages: 239-45
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20817032
- DOI: http://dx.doi.org/10.1016/j.jneumeth.2010.08.022
Medical and Biotech [MESH] Definitions
Neurulation
An early embryonic developmental process of CHORDATES that is characterized by morphogenic movements of ECTODERM resulting in the formation of the NEURAL PLATE; the NEURAL CREST; and the NEURAL TUBE. Improper closure of the NEURAL GROOVE results in congenital NEURAL TUBE DEFECTS.
Neural Stem Cells
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Stage-specific Embryonic Antigens
Cell-surface molecules that exhibit lineage-restricted patterns of expression during EMBRYONIC DEVELOPMENT. The antigens are useful markers in the identification of EMBRYONIC STEM CELLS.
Brain
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Embryonal Carcinoma Stem Cells
The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.
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