Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol
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2011
Authors
Talens-Visconti, RaquelSanchez-Vera, Irene
Perić, Jelena
Amparo Perez-Arago, Maria
Erceg, Slaven
Stojković, Miodrag
Guerri, Consuelo
Article (Published version)
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The in vitro generation of neural cells from human embryonic stem cells is a powerful tool to acquire better knowledge of the cellular and molecular events involved in early human neural and brain development under physiological and pathological conditions. Prenatal alcohol exposure can induce important anomalies in the developing brain, the embryogenesis being an important critical period for the craniofacial defects and mental disabilities associated with fetal alcohol syndrome. Here, we report the generation of neural progenitors (NPs) from human embryonic stem cells. Neuroepithelial progenitors display the morphological and functional characteristics of their embryonic counterparts and the proper timing of neurons and glia cells generation. Immunocytochemical and real time (RT)-polymerase chain reaction analyses reveal that cells appeared as clusters during neuroepithelial cell proliferation and that the genes associated with the neuroectodermal (Pax-6) and the endodermic (alpha-fe...toprotein) lineages decreased in parallel to the upregulation of the genes of NPs (nestin and Tuj1), followed by their differentiation into neurons (MAP-2+, GABA+), oligodendrocytes [galactocerebroside (GalC+)], and astrocytes (GFAP+). We further demonstrate, for the first time, that human NPs express the endocannabinoid receptors (CB1 and CB2) and the enzymes involved in endocannabinoids synthesis (NAPE-PLD) and degradation (FAAH). Using this in vitro culture, we demonstrate that ethanol exposure impairs NPs survival, affects the differentiation of NPs into neurons and astrocytes, disrupts the actin cytoskeleton, and affects the expression of different genes associated with neural differentiation. The results provide new insights into the effects of ethanol on human embryogenesis and neuroprogenitors and offer an opportunity to delineate potential therapeutic strategies to restore early ethanol-induced brain damage.
Source:
Stem Cells and Development, 2011, 20, 2, 327-339Publisher:
- Mary Ann Liebert, Inc, New Rochelle
Funding / projects:
- PNSD, Spanish Ministry of Health
- RTA Network [G03/005]
- Carlos III Institute
- Direc. Gen. of Drugdependence (GV)
- Regerenative-Medicine grant (Generakitat Valenciana and Carlos III Institute)
DOI: 10.1089/scd.2010.0037
ISSN: 1547-3287
PubMed: 20491543
WoS: 000286460000013
Scopus: 2-s2.0-78951487307
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Talens-Visconti, Raquel AU - Sanchez-Vera, Irene AU - Perić, Jelena AU - Amparo Perez-Arago, Maria AU - Erceg, Slaven AU - Stojković, Miodrag AU - Guerri, Consuelo PY - 2011 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/478 AB - The in vitro generation of neural cells from human embryonic stem cells is a powerful tool to acquire better knowledge of the cellular and molecular events involved in early human neural and brain development under physiological and pathological conditions. Prenatal alcohol exposure can induce important anomalies in the developing brain, the embryogenesis being an important critical period for the craniofacial defects and mental disabilities associated with fetal alcohol syndrome. Here, we report the generation of neural progenitors (NPs) from human embryonic stem cells. Neuroepithelial progenitors display the morphological and functional characteristics of their embryonic counterparts and the proper timing of neurons and glia cells generation. Immunocytochemical and real time (RT)-polymerase chain reaction analyses reveal that cells appeared as clusters during neuroepithelial cell proliferation and that the genes associated with the neuroectodermal (Pax-6) and the endodermic (alpha-fetoprotein) lineages decreased in parallel to the upregulation of the genes of NPs (nestin and Tuj1), followed by their differentiation into neurons (MAP-2+, GABA+), oligodendrocytes [galactocerebroside (GalC+)], and astrocytes (GFAP+). We further demonstrate, for the first time, that human NPs express the endocannabinoid receptors (CB1 and CB2) and the enzymes involved in endocannabinoids synthesis (NAPE-PLD) and degradation (FAAH). Using this in vitro culture, we demonstrate that ethanol exposure impairs NPs survival, affects the differentiation of NPs into neurons and astrocytes, disrupts the actin cytoskeleton, and affects the expression of different genes associated with neural differentiation. The results provide new insights into the effects of ethanol on human embryogenesis and neuroprogenitors and offer an opportunity to delineate potential therapeutic strategies to restore early ethanol-induced brain damage. PB - Mary Ann Liebert, Inc, New Rochelle T2 - Stem Cells and Development T1 - Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol EP - 339 IS - 2 SP - 327 VL - 20 DO - 10.1089/scd.2010.0037 ER -
@article{ author = "Talens-Visconti, Raquel and Sanchez-Vera, Irene and Perić, Jelena and Amparo Perez-Arago, Maria and Erceg, Slaven and Stojković, Miodrag and Guerri, Consuelo", year = "2011", abstract = "The in vitro generation of neural cells from human embryonic stem cells is a powerful tool to acquire better knowledge of the cellular and molecular events involved in early human neural and brain development under physiological and pathological conditions. Prenatal alcohol exposure can induce important anomalies in the developing brain, the embryogenesis being an important critical period for the craniofacial defects and mental disabilities associated with fetal alcohol syndrome. Here, we report the generation of neural progenitors (NPs) from human embryonic stem cells. Neuroepithelial progenitors display the morphological and functional characteristics of their embryonic counterparts and the proper timing of neurons and glia cells generation. Immunocytochemical and real time (RT)-polymerase chain reaction analyses reveal that cells appeared as clusters during neuroepithelial cell proliferation and that the genes associated with the neuroectodermal (Pax-6) and the endodermic (alpha-fetoprotein) lineages decreased in parallel to the upregulation of the genes of NPs (nestin and Tuj1), followed by their differentiation into neurons (MAP-2+, GABA+), oligodendrocytes [galactocerebroside (GalC+)], and astrocytes (GFAP+). We further demonstrate, for the first time, that human NPs express the endocannabinoid receptors (CB1 and CB2) and the enzymes involved in endocannabinoids synthesis (NAPE-PLD) and degradation (FAAH). Using this in vitro culture, we demonstrate that ethanol exposure impairs NPs survival, affects the differentiation of NPs into neurons and astrocytes, disrupts the actin cytoskeleton, and affects the expression of different genes associated with neural differentiation. The results provide new insights into the effects of ethanol on human embryogenesis and neuroprogenitors and offer an opportunity to delineate potential therapeutic strategies to restore early ethanol-induced brain damage.", publisher = "Mary Ann Liebert, Inc, New Rochelle", journal = "Stem Cells and Development", title = "Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol", pages = "339-327", number = "2", volume = "20", doi = "10.1089/scd.2010.0037" }
Talens-Visconti, R., Sanchez-Vera, I., Perić, J., Amparo Perez-Arago, M., Erceg, S., Stojković, M.,& Guerri, C.. (2011). Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol. in Stem Cells and Development Mary Ann Liebert, Inc, New Rochelle., 20(2), 327-339. https://doi.org/10.1089/scd.2010.0037
Talens-Visconti R, Sanchez-Vera I, Perić J, Amparo Perez-Arago M, Erceg S, Stojković M, Guerri C. Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol. in Stem Cells and Development. 2011;20(2):327-339. doi:10.1089/scd.2010.0037 .
Talens-Visconti, Raquel, Sanchez-Vera, Irene, Perić, Jelena, Amparo Perez-Arago, Maria, Erceg, Slaven, Stojković, Miodrag, Guerri, Consuelo, "Neural Differentiation from Human Embryonic Stem Cells as a Tool to Study Early Brain Development and the Neuroteratogenic Effects of Ethanol" in Stem Cells and Development, 20, no. 2 (2011):327-339, https://doi.org/10.1089/scd.2010.0037 . .