Limits...
Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Bakken TE, Miller JA, Luo R, Bernard A, Bennett JL, Lee CK, Bertagnolli D, Parikshak NN, Smith KA, Sunkin SM, Amaral DG, Geschwind DH, Lein ES - Hum. Mol. Genet. (2015)

Bottom Line: Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex.In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes.This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

View Article: PubMed Central - PubMed

Affiliation: Allen Institute for Brain Science, Seattle, WA, USA.

No MeSH data available.


Related in: MedlinePlus

Gene expression is associated with both brain region and development stages. (A) MDS using all genes shows that samples cluster by both region (x-axis) and age (y-axis). Brain regions are illustrated by different shapes, while ages are labeled by different colors. The x- and y-axes represent the first and second PC, respectively, with the percent variance explained by each coordinate in parentheses. (B and C) Heatmap of top 1000 ANOVA genes for age (B) and region (C). Genes are hierarchically clustered along the x-axis, and gene clusters associated with different ages and regions are labeled by horizontal color bars. Samples are clustered along the y-axis and are color coded based both on region (left vertical bars) and age (right vertical bars).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492396&req=5

DDV166F1: Gene expression is associated with both brain region and development stages. (A) MDS using all genes shows that samples cluster by both region (x-axis) and age (y-axis). Brain regions are illustrated by different shapes, while ages are labeled by different colors. The x- and y-axes represent the first and second PC, respectively, with the percent variance explained by each coordinate in parentheses. (B and C) Heatmap of top 1000 ANOVA genes for age (B) and region (C). Genes are hierarchically clustered along the x-axis, and gene clusters associated with different ages and regions are labeled by horizontal color bars. Samples are clustered along the y-axis and are color coded based both on region (left vertical bars) and age (right vertical bars).

Mentions: To explore the relationship between gene expression and spatiotemporal dynamics in the rhesus monkey brain, we calculated the distance between brain samples based on their correlated expression patterns and performed classical multidimensional scaling (MDS) to represent these distances in two dimensions. We found that the first two principal coordinates (PCs) corresponded to brain region and age (Fig. 1A), and explained more than half of the transcriptional variation between brain samples (37 and 24%). To identify specific genes differentially expressed (DE) between brain regions or changing across postnatal development, we performed two one-way ANOVAs on all samples, using age and brain region as the two factors. We found that 10 338 of 32 217 (32%) probes were DE [false discovery rate (FDR) < 0.01] across developmental stages, and 13 527 (42%) probes were DE across brain regions. A total of 2967 probes (representing 2141 genes) were DE across both development and brain regions (Supplementary Material, Table S2) and were significantly enriched for several neurodevelopmental gene ontology (GO) categories including axon guidance (nominal P = 3.4 × 10−7), neuron projection (P = 1.8 × 10−6) and synapse (P = 2.0 × 10−5). Next, we searched for age-specific changes in expression and found 5935 DE probes (FDR < 0.05, >2 fold-change between pairs of ages for any region). The vast majority were DE at birth (3492 probes) or adulthood (1569) with many fewer at intermediate ages (149 at T = 3, 725 at T = 12; for a full list of age-related genes, see Supplementary Material, Table S2).Figure 1.


Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Bakken TE, Miller JA, Luo R, Bernard A, Bennett JL, Lee CK, Bertagnolli D, Parikshak NN, Smith KA, Sunkin SM, Amaral DG, Geschwind DH, Lein ES - Hum. Mol. Genet. (2015)

Gene expression is associated with both brain region and development stages. (A) MDS using all genes shows that samples cluster by both region (x-axis) and age (y-axis). Brain regions are illustrated by different shapes, while ages are labeled by different colors. The x- and y-axes represent the first and second PC, respectively, with the percent variance explained by each coordinate in parentheses. (B and C) Heatmap of top 1000 ANOVA genes for age (B) and region (C). Genes are hierarchically clustered along the x-axis, and gene clusters associated with different ages and regions are labeled by horizontal color bars. Samples are clustered along the y-axis and are color coded based both on region (left vertical bars) and age (right vertical bars).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492396&req=5

DDV166F1: Gene expression is associated with both brain region and development stages. (A) MDS using all genes shows that samples cluster by both region (x-axis) and age (y-axis). Brain regions are illustrated by different shapes, while ages are labeled by different colors. The x- and y-axes represent the first and second PC, respectively, with the percent variance explained by each coordinate in parentheses. (B and C) Heatmap of top 1000 ANOVA genes for age (B) and region (C). Genes are hierarchically clustered along the x-axis, and gene clusters associated with different ages and regions are labeled by horizontal color bars. Samples are clustered along the y-axis and are color coded based both on region (left vertical bars) and age (right vertical bars).
Mentions: To explore the relationship between gene expression and spatiotemporal dynamics in the rhesus monkey brain, we calculated the distance between brain samples based on their correlated expression patterns and performed classical multidimensional scaling (MDS) to represent these distances in two dimensions. We found that the first two principal coordinates (PCs) corresponded to brain region and age (Fig. 1A), and explained more than half of the transcriptional variation between brain samples (37 and 24%). To identify specific genes differentially expressed (DE) between brain regions or changing across postnatal development, we performed two one-way ANOVAs on all samples, using age and brain region as the two factors. We found that 10 338 of 32 217 (32%) probes were DE [false discovery rate (FDR) < 0.01] across developmental stages, and 13 527 (42%) probes were DE across brain regions. A total of 2967 probes (representing 2141 genes) were DE across both development and brain regions (Supplementary Material, Table S2) and were significantly enriched for several neurodevelopmental gene ontology (GO) categories including axon guidance (nominal P = 3.4 × 10−7), neuron projection (P = 1.8 × 10−6) and synapse (P = 2.0 × 10−5). Next, we searched for age-specific changes in expression and found 5935 DE probes (FDR < 0.05, >2 fold-change between pairs of ages for any region). The vast majority were DE at birth (3492 probes) or adulthood (1569) with many fewer at intermediate ages (149 at T = 3, 725 at T = 12; for a full list of age-related genes, see Supplementary Material, Table S2).Figure 1.

Bottom Line: Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex.In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes.This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

View Article: PubMed Central - PubMed

Affiliation: Allen Institute for Brain Science, Seattle, WA, USA.

No MeSH data available.


Related in: MedlinePlus