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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

Summary of differential splicing events identified by RNA-Seq. (a) Number (percentage in parentheses) of exons with differential inclusion levels ((Δ/Ψ/ > 0.1, FDR < 0.1) between given tissue pairs. (b) Venn diagrams showing the distribution and overlap of exons (left) and genes (right) in the three placental tissues that are differentially spliced between the placental and non-placental tissues.
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Figure 4: Summary of differential splicing events identified by RNA-Seq. (a) Number (percentage in parentheses) of exons with differential inclusion levels ((Δ/Ψ/ > 0.1, FDR < 0.1) between given tissue pairs. (b) Venn diagrams showing the distribution and overlap of exons (left) and genes (right) in the three placental tissues that are differentially spliced between the placental and non-placental tissues.

Mentions: To directly identify AS differences between the placenta and other human tissues, we calculated the exon inclusion level (Ψ) of alternatively spliced cassette exons in each tissue using RNA-Seq reads that are uniquely mapped to the upstream, downstream, and skipping exon-exon junctions of alternatively spliced exons as previously described [13]. We used a Bayesian approach MATS (Multivariate Analysis of Differential Splicing) [48] to perform pairwise comparisons of tissue pairs to test if the difference in Ψ of any alternatively spliced exon between two tissues exceeds 10% (see Methods for details). Between the three compartments of the placenta, approximately 0.1% of exons were found to be differentially spliced (FDR < 0.1). In contrast, there was a much greater degree of splicing difference between placental and other human tissues, with 1.6% of exons, on average, being differentially spliced between one of the placental tissues and one of the 16 HBM2.0 tissues (Figure 4a). It should be noted that given the moderate sequencing depth of 50-83 million reads per tissue, this analysis is expected to have an appreciable level of false negatives. The true extent of splicing differences among these tissues could be considerably larger.


Transcriptome landscape of the human placenta.

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

Summary of differential splicing events identified by RNA-Seq. (a) Number (percentage in parentheses) of exons with differential inclusion levels ((Δ/Ψ/ > 0.1, FDR < 0.1) between given tissue pairs. (b) Venn diagrams showing the distribution and overlap of exons (left) and genes (right) in the three placental tissues that are differentially spliced between the placental and non-placental tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Summary of differential splicing events identified by RNA-Seq. (a) Number (percentage in parentheses) of exons with differential inclusion levels ((Δ/Ψ/ > 0.1, FDR < 0.1) between given tissue pairs. (b) Venn diagrams showing the distribution and overlap of exons (left) and genes (right) in the three placental tissues that are differentially spliced between the placental and non-placental tissues.
Mentions: To directly identify AS differences between the placenta and other human tissues, we calculated the exon inclusion level (Ψ) of alternatively spliced cassette exons in each tissue using RNA-Seq reads that are uniquely mapped to the upstream, downstream, and skipping exon-exon junctions of alternatively spliced exons as previously described [13]. We used a Bayesian approach MATS (Multivariate Analysis of Differential Splicing) [48] to perform pairwise comparisons of tissue pairs to test if the difference in Ψ of any alternatively spliced exon between two tissues exceeds 10% (see Methods for details). Between the three compartments of the placenta, approximately 0.1% of exons were found to be differentially spliced (FDR < 0.1). In contrast, there was a much greater degree of splicing difference between placental and other human tissues, with 1.6% of exons, on average, being differentially spliced between one of the placental tissues and one of the 16 HBM2.0 tissues (Figure 4a). It should be noted that given the moderate sequencing depth of 50-83 million reads per tissue, this analysis is expected to have an appreciable level of false negatives. The true extent of splicing differences among these tissues could be considerably larger.

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