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Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus.

Amarger V, Lecouillard A, Ancellet L, Grit I, Castellano B, Hulin P, Parnet P - Nutrients (2014)

Bottom Line: Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells.Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII.Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. valerie.amarger@univ-nantes.fr.

ABSTRACT
Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.

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DNA methylation analysis of the Gfap and S100β genes in cultured NPCs treated with SAM and 5-AZA. (A) The methylation level of the CpG sites at position –429 in the Gfap promoter and –276 in the S100β promoter. (B) The methylation level of five CpG sites at positions 8, 14, 29, 32 and 49 in Gfap exon 1. (n = 2 different well cultures per treatment).
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nutrients-06-04200-f008: DNA methylation analysis of the Gfap and S100β genes in cultured NPCs treated with SAM and 5-AZA. (A) The methylation level of the CpG sites at position –429 in the Gfap promoter and –276 in the S100β promoter. (B) The methylation level of five CpG sites at positions 8, 14, 29, 32 and 49 in Gfap exon 1. (n = 2 different well cultures per treatment).

Mentions: The two CpG sites situated in the Gfap and S100β gene promoters were hypomethylated (around 5% and 9% for Gfap and S100β, respectively) (Figure 8), and there was no difference between the treatments; however, because of the low number of cultures (n = 2 per treatment), we did not perform any statistical analysis. The methylation profile of the Gfap exon 1 on cultured cells was identical to the one observed in the hippocampus at birth, although the overall methylation level was lower (Figure 8). The cells treated with SAM had a slightly higher level of methylation for the five CpGs, whereas there was no difference between the control and 5-AZA-treated cells.


Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus.

Amarger V, Lecouillard A, Ancellet L, Grit I, Castellano B, Hulin P, Parnet P - Nutrients (2014)

DNA methylation analysis of the Gfap and S100β genes in cultured NPCs treated with SAM and 5-AZA. (A) The methylation level of the CpG sites at position –429 in the Gfap promoter and –276 in the S100β promoter. (B) The methylation level of five CpG sites at positions 8, 14, 29, 32 and 49 in Gfap exon 1. (n = 2 different well cultures per treatment).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210914&req=5

nutrients-06-04200-f008: DNA methylation analysis of the Gfap and S100β genes in cultured NPCs treated with SAM and 5-AZA. (A) The methylation level of the CpG sites at position –429 in the Gfap promoter and –276 in the S100β promoter. (B) The methylation level of five CpG sites at positions 8, 14, 29, 32 and 49 in Gfap exon 1. (n = 2 different well cultures per treatment).
Mentions: The two CpG sites situated in the Gfap and S100β gene promoters were hypomethylated (around 5% and 9% for Gfap and S100β, respectively) (Figure 8), and there was no difference between the treatments; however, because of the low number of cultures (n = 2 per treatment), we did not perform any statistical analysis. The methylation profile of the Gfap exon 1 on cultured cells was identical to the one observed in the hippocampus at birth, although the overall methylation level was lower (Figure 8). The cells treated with SAM had a slightly higher level of methylation for the five CpGs, whereas there was no difference between the control and 5-AZA-treated cells.

Bottom Line: Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells.Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII.Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. valerie.amarger@univ-nantes.fr.

ABSTRACT
Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.

Show MeSH