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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

Hierarchical clustering analysis of differentially expressed genes among placental and other human tissues. We calculated expression levels of 51,682 Ensembl genes in each tissue and selected those expressed with FPKM > 5 in 8 or more tissues, which were then ranked based on their coefficient of variation (CV). The heat map was generated by average linkage hierarchical clustering of the top 1,000 differentially expressed genes, using 1-Pearson correlation coefficient as the distance metric. Scaled expression values are color-coded according to the legend in the top left corner.
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Figure 1: Hierarchical clustering analysis of differentially expressed genes among placental and other human tissues. We calculated expression levels of 51,682 Ensembl genes in each tissue and selected those expressed with FPKM > 5 in 8 or more tissues, which were then ranked based on their coefficient of variation (CV). The heat map was generated by average linkage hierarchical clustering of the top 1,000 differentially expressed genes, using 1-Pearson correlation coefficient as the distance metric. Scaled expression values are color-coded according to the legend in the top left corner.

Mentions: Using the uniquely mapped read pairs, we estimated the expression levels of 22,523 protein-coding genes (Ensembl genes, r57) in each tissue using the "Fragments Per Kilobase of gene per Million mapped fragments" (FPKM) metric [21] in a way similar to RPKM [22] (see details in Methods). With a coverage depth ranging from 50 to 80 million paired-end reads per tissue, we detected the expression (i.e. FPKM > 0) of the majority of the protein-coding genes (66-84% for each of the 19 tissues). Approximately half of the genes were expressed with FPKM > 1 (Table S2 and Figure S1 in Additional file 1). We investigated the similarity in the global gene expression profiles among the three placental compartments and 16 HBM2.0 tissues using average linkage hierarchical clustering of the top 1,000 most divergent genes (Figure 1). The three placental tissues clustered more closely with one another than with the other 16 tissues, suggesting the existence of a placenta-specific gene expression signature. In addition, we also observed genes with distinct expression patterns among amnion, chorion, and decidua, indicating that each compartment of the placenta has its unique expression signature, possibly reflecting differences in their functions and/or biological activities.


Transcriptome landscape of the human placenta.

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

Hierarchical clustering analysis of differentially expressed genes among placental and other human tissues. We calculated expression levels of 51,682 Ensembl genes in each tissue and selected those expressed with FPKM > 5 in 8 or more tissues, which were then ranked based on their coefficient of variation (CV). The heat map was generated by average linkage hierarchical clustering of the top 1,000 differentially expressed genes, using 1-Pearson correlation coefficient as the distance metric. Scaled expression values are color-coded according to the legend in the top left corner.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Hierarchical clustering analysis of differentially expressed genes among placental and other human tissues. We calculated expression levels of 51,682 Ensembl genes in each tissue and selected those expressed with FPKM > 5 in 8 or more tissues, which were then ranked based on their coefficient of variation (CV). The heat map was generated by average linkage hierarchical clustering of the top 1,000 differentially expressed genes, using 1-Pearson correlation coefficient as the distance metric. Scaled expression values are color-coded according to the legend in the top left corner.
Mentions: Using the uniquely mapped read pairs, we estimated the expression levels of 22,523 protein-coding genes (Ensembl genes, r57) in each tissue using the "Fragments Per Kilobase of gene per Million mapped fragments" (FPKM) metric [21] in a way similar to RPKM [22] (see details in Methods). With a coverage depth ranging from 50 to 80 million paired-end reads per tissue, we detected the expression (i.e. FPKM > 0) of the majority of the protein-coding genes (66-84% for each of the 19 tissues). Approximately half of the genes were expressed with FPKM > 1 (Table S2 and Figure S1 in Additional file 1). We investigated the similarity in the global gene expression profiles among the three placental compartments and 16 HBM2.0 tissues using average linkage hierarchical clustering of the top 1,000 most divergent genes (Figure 1). The three placental tissues clustered more closely with one another than with the other 16 tissues, suggesting the existence of a placenta-specific gene expression signature. In addition, we also observed genes with distinct expression patterns among amnion, chorion, and decidua, indicating that each compartment of the placenta has its unique expression signature, possibly reflecting differences in their functions and/or biological activities.

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