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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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Expression profile of splicing factors in placental and other human tissues. (a) Heat map showing the expression levels of 60 selected splicing factors across all 19 tissues. Scaled expression values are color-coded according to the legend in the top left corner. Clustering of genes and tissues are both generated by average linkage hierarchical clustering using 1-Pearson correlation coefficient as the distance metric. (b) Expression levels of 3 splicing factors differentially expressed between placental and other human tissues. Each bar labeled HBM2.0 (in blue) represents mean expression value of all 16 HBM2.0 tissues.
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Figure 3: Expression profile of splicing factors in placental and other human tissues. (a) Heat map showing the expression levels of 60 selected splicing factors across all 19 tissues. Scaled expression values are color-coded according to the legend in the top left corner. Clustering of genes and tissues are both generated by average linkage hierarchical clustering using 1-Pearson correlation coefficient as the distance metric. (b) Expression levels of 3 splicing factors differentially expressed between placental and other human tissues. Each bar labeled HBM2.0 (in blue) represents mean expression value of all 16 HBM2.0 tissues.

Mentions: To identify SFs with a placenta-specific increase or decrease in expression levels, we compiled a list of sixty well-studied SFs [14,45], and analyzed their RNA-Seq FPKM gene expression levels in the placenta and 16 other human tissues. Hierarchical clustering of the 60 SFs revealed a sub-cluster among the three placental compartments, (Figure 3a), consistent with the clustering pattern based on all genes (Figure 1). This cluster analysis recapitulated the known tissue-specific expression patterns of SFs, such as the brain-specific expression of NOVA1, NOVA2, FOX1 (also known as A2BP1), and BRUNOL4. Interestingly, we identified several SFs with compartment-specific changes in expression levels in the placenta, most notably ESRP1 (in amnion) and MBNL3 (in decidua) (Figure 3b), which we confirmed by qRT-PCR (Figure S2 in Additional file 1). ESRP1 and MBNL3 are known to regulate splicing of a large number of genes in epithelial cells [46] and during myogenic differentiation [47], suggesting a unique set of AS events in individual placental compartments downstream of these master splicing regulators. We also identified several ubiquitously expressed SFs with a significant difference in expression levels among the three placental compartments. For example, FOX2 (also known as RBM9), an important splicing regulator in the heart, muscle, and neurons [14], was expressed two-fold higher in amnion compared to chorion and decidua. Together, the expression profiles of SFs suggest tissue-specific regulation of AS between the placenta and other tissues and between different compartments of the placenta.


Transcriptome landscape of the human placenta.

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

Expression profile of splicing factors in placental and other human tissues. (a) Heat map showing the expression levels of 60 selected splicing factors across all 19 tissues. Scaled expression values are color-coded according to the legend in the top left corner. Clustering of genes and tissues are both generated by average linkage hierarchical clustering using 1-Pearson correlation coefficient as the distance metric. (b) Expression levels of 3 splicing factors differentially expressed between placental and other human tissues. Each bar labeled HBM2.0 (in blue) represents mean expression value of all 16 HBM2.0 tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Expression profile of splicing factors in placental and other human tissues. (a) Heat map showing the expression levels of 60 selected splicing factors across all 19 tissues. Scaled expression values are color-coded according to the legend in the top left corner. Clustering of genes and tissues are both generated by average linkage hierarchical clustering using 1-Pearson correlation coefficient as the distance metric. (b) Expression levels of 3 splicing factors differentially expressed between placental and other human tissues. Each bar labeled HBM2.0 (in blue) represents mean expression value of all 16 HBM2.0 tissues.
Mentions: To identify SFs with a placenta-specific increase or decrease in expression levels, we compiled a list of sixty well-studied SFs [14,45], and analyzed their RNA-Seq FPKM gene expression levels in the placenta and 16 other human tissues. Hierarchical clustering of the 60 SFs revealed a sub-cluster among the three placental compartments, (Figure 3a), consistent with the clustering pattern based on all genes (Figure 1). This cluster analysis recapitulated the known tissue-specific expression patterns of SFs, such as the brain-specific expression of NOVA1, NOVA2, FOX1 (also known as A2BP1), and BRUNOL4. Interestingly, we identified several SFs with compartment-specific changes in expression levels in the placenta, most notably ESRP1 (in amnion) and MBNL3 (in decidua) (Figure 3b), which we confirmed by qRT-PCR (Figure S2 in Additional file 1). ESRP1 and MBNL3 are known to regulate splicing of a large number of genes in epithelial cells [46] and during myogenic differentiation [47], suggesting a unique set of AS events in individual placental compartments downstream of these master splicing regulators. We also identified several ubiquitously expressed SFs with a significant difference in expression levels among the three placental compartments. For example, FOX2 (also known as RBM9), an important splicing regulator in the heart, muscle, and neurons [14], was expressed two-fold higher in amnion compared to chorion and decidua. Together, the expression profiles of SFs suggest tissue-specific regulation of AS between the placenta and other tissues and between different compartments of the placenta.

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