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Transcriptome landscape of the human placenta.

Kim J, Zhao K, Jiang P, Lu ZX, Wang J, Murray JC, Xing Y - BMC Genomics (2012)

Bottom Line: The master splicing regulator ESRP1 is expressed at a proportionately higher level in amnion compared to all other analyzed human tissues, and there is a significant enrichment of ESRP1-regulated exons with tissue-specific splicing activities in amnion.Importantly, genes with differential expression or splicing in the placenta are significantly enriched for genes implicated in placental abnormalities and preterm birth.These data are publicly available providing the community with a rich resource for placental physiology and disease-related studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA52242, USA.

ABSTRACT

Background: The placenta is a key component in understanding the physiological processes involved in pregnancy. Characterizing genes critical for placental function can serve as a basis for identifying mechanisms underlying both normal and pathologic pregnancies. Detailing the placental tissue transcriptome could provide a valuable resource for genomic studies related to placental disease.

Results: We have conducted a deep RNA sequencing (RNA-Seq) study on three tissue components (amnion, chorion, and decidua) of 5 human placentas from normal term pregnancies. We compared the placental RNA-Seq data to that of 16 other human tissues and observed a wide spectrum of transcriptome differences both between placenta and other human tissues and between distinct compartments of the placenta. Exon-level analysis of the RNA-Seq data revealed a large number of exons with differential splicing activities between placenta and other tissues, and 79% (27 out of 34) of the events selected for RT-PCR test were validated. The master splicing regulator ESRP1 is expressed at a proportionately higher level in amnion compared to all other analyzed human tissues, and there is a significant enrichment of ESRP1-regulated exons with tissue-specific splicing activities in amnion. This suggests an important role of alternative splicing in regulating gene function and activity in specific placental compartments. Importantly, genes with differential expression or splicing in the placenta are significantly enriched for genes implicated in placental abnormalities and preterm birth. In addition, we identified 604-1007 novel transcripts and 494-585 novel exons expressed in each of the three placental compartments.

Conclusions: Our data demonstrate unique aspects of gene expression and splicing in placental tissues that provide a basis for disease investigation related to disruption of these mechanisms. These data are publicly available providing the community with a rich resource for placental physiology and disease-related studies.

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Related in: MedlinePlus

Functional interaction network analysis of genes with enriched expression (EE) and differential splicing (DS) in the placenta. Shown is module 0 of the interaction network constructed for chorion. Circular node: a query gene. Diamond-shaped node: a linker gene. Node color was determined based on whether the query gene shows EE (green), DS (pink), or both (red). Two large circular clusters represent highlighted significantly enriched pathways in chorion: glypican, SMAD2/3, and TGF-beta receptor signaling pathways (left-hand side; red lines) and HIF-1 alpha transcription factor signaling pathway (right-hand side; blue lines). FOS and SERPINE1 are shared by both groups of enriched pathways, but only shown in the right cluster. Several linker hub genes with dense connections with the highlighted pathways are also shown in bigger nodes.
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Figure 7: Functional interaction network analysis of genes with enriched expression (EE) and differential splicing (DS) in the placenta. Shown is module 0 of the interaction network constructed for chorion. Circular node: a query gene. Diamond-shaped node: a linker gene. Node color was determined based on whether the query gene shows EE (green), DS (pink), or both (red). Two large circular clusters represent highlighted significantly enriched pathways in chorion: glypican, SMAD2/3, and TGF-beta receptor signaling pathways (left-hand side; red lines) and HIF-1 alpha transcription factor signaling pathway (right-hand side; blue lines). FOS and SERPINE1 are shared by both groups of enriched pathways, but only shown in the right cluster. Several linker hub genes with dense connections with the highlighted pathways are also shown in bigger nodes.

Mentions: The results of our analysis performed on each of the three placental tissues showed significant enrichment of many functional pathways (Table S3 in Additional file 2), including those involved in the regulation of SMAD2/3 signaling, TGF-beta receptor signaling, and HIF-1 alpha TF network, which were significantly overrepresented in module 0 of all the amnion, chorion, and decidua FI networks (shown in Figure 7 is module 0 of the chorion FI network).


Transcriptome landscape of the human placenta.

Kim J, Zhao K, Jiang P, Lu ZX, Wang J, Murray JC, Xing Y - BMC Genomics (2012)

Functional interaction network analysis of genes with enriched expression (EE) and differential splicing (DS) in the placenta. Shown is module 0 of the interaction network constructed for chorion. Circular node: a query gene. Diamond-shaped node: a linker gene. Node color was determined based on whether the query gene shows EE (green), DS (pink), or both (red). Two large circular clusters represent highlighted significantly enriched pathways in chorion: glypican, SMAD2/3, and TGF-beta receptor signaling pathways (left-hand side; red lines) and HIF-1 alpha transcription factor signaling pathway (right-hand side; blue lines). FOS and SERPINE1 are shared by both groups of enriched pathways, but only shown in the right cluster. Several linker hub genes with dense connections with the highlighted pathways are also shown in bigger nodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368734&req=5

Figure 7: Functional interaction network analysis of genes with enriched expression (EE) and differential splicing (DS) in the placenta. Shown is module 0 of the interaction network constructed for chorion. Circular node: a query gene. Diamond-shaped node: a linker gene. Node color was determined based on whether the query gene shows EE (green), DS (pink), or both (red). Two large circular clusters represent highlighted significantly enriched pathways in chorion: glypican, SMAD2/3, and TGF-beta receptor signaling pathways (left-hand side; red lines) and HIF-1 alpha transcription factor signaling pathway (right-hand side; blue lines). FOS and SERPINE1 are shared by both groups of enriched pathways, but only shown in the right cluster. Several linker hub genes with dense connections with the highlighted pathways are also shown in bigger nodes.
Mentions: The results of our analysis performed on each of the three placental tissues showed significant enrichment of many functional pathways (Table S3 in Additional file 2), including those involved in the regulation of SMAD2/3 signaling, TGF-beta receptor signaling, and HIF-1 alpha TF network, which were significantly overrepresented in module 0 of all the amnion, chorion, and decidua FI networks (shown in Figure 7 is module 0 of the chorion FI network).

Bottom Line: The master splicing regulator ESRP1 is expressed at a proportionately higher level in amnion compared to all other analyzed human tissues, and there is a significant enrichment of ESRP1-regulated exons with tissue-specific splicing activities in amnion.Importantly, genes with differential expression or splicing in the placenta are significantly enriched for genes implicated in placental abnormalities and preterm birth.These data are publicly available providing the community with a rich resource for placental physiology and disease-related studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA52242, USA.

ABSTRACT

Background: The placenta is a key component in understanding the physiological processes involved in pregnancy. Characterizing genes critical for placental function can serve as a basis for identifying mechanisms underlying both normal and pathologic pregnancies. Detailing the placental tissue transcriptome could provide a valuable resource for genomic studies related to placental disease.

Results: We have conducted a deep RNA sequencing (RNA-Seq) study on three tissue components (amnion, chorion, and decidua) of 5 human placentas from normal term pregnancies. We compared the placental RNA-Seq data to that of 16 other human tissues and observed a wide spectrum of transcriptome differences both between placenta and other human tissues and between distinct compartments of the placenta. Exon-level analysis of the RNA-Seq data revealed a large number of exons with differential splicing activities between placenta and other tissues, and 79% (27 out of 34) of the events selected for RT-PCR test were validated. The master splicing regulator ESRP1 is expressed at a proportionately higher level in amnion compared to all other analyzed human tissues, and there is a significant enrichment of ESRP1-regulated exons with tissue-specific splicing activities in amnion. This suggests an important role of alternative splicing in regulating gene function and activity in specific placental compartments. Importantly, genes with differential expression or splicing in the placenta are significantly enriched for genes implicated in placental abnormalities and preterm birth. In addition, we identified 604-1007 novel transcripts and 494-585 novel exons expressed in each of the three placental compartments.

Conclusions: Our data demonstrate unique aspects of gene expression and splicing in placental tissues that provide a basis for disease investigation related to disruption of these mechanisms. These data are publicly available providing the community with a rich resource for placental physiology and disease-related studies.

Show MeSH
Related in: MedlinePlus