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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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An example of novel transcriptional active regions (TARs) identified in the present study. Shown is a novel TAR on chromosome 16 found in amnion. A wiggle plot of RNA-Seq read coverage, structures of 3 alternatively spliced transcripts and ESTs were shown from top to bottom. Note that there is no gene annotated in this region in the indicated annotation databases.
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Figure 8: An example of novel transcriptional active regions (TARs) identified in the present study. Shown is a novel TAR on chromosome 16 found in amnion. A wiggle plot of RNA-Seq read coverage, structures of 3 alternatively spliced transcripts and ESTs were shown from top to bottom. Note that there is no gene annotated in this region in the indicated annotation databases.

Mentions: One major advantage of RNA-Seq compared to microarray technology is its capability to detect un-annotated novel transcripts. To identify novel transcriptional active regions (TARs) in placental tissues, we used the software Scripture [56] for ab initio reconstruction of transcripts for each tissue after sequence mapping with Tophat [21] (see details in Methods). We identified approximately 100,000 transcripts in each of the placental tissues with more than 70% of them being multi-exon transcripts (Table 2). To reduce false signals, only multiexon transcripts were used in the following analysis. After overlapping transcripts were merged into one single TAR, a total of 13,469, 16,987, and 15,158 TARs were found in amnion, chorion, and decidua, respectively. We filtered out the ones overlapping with the annotated transcripts from the NCBI RefSeq, UCSC, Ensembl, and Vega database and identified 604, 1,007, and 896 novel TARs in amnion, chorion, and decidua, respectively. The expression levels of the identified novel TARs are listed in Table S4 in Additional file 3. Importantly, a large proportion of these novel TARs (285, 456, and 468 in the corresponding placental tissues) are placenta-specific or more than 4 fold enriched compared to non-placental tissues. Shown in Figure 8 is one example of novel TARs on chromosome 16 (chr16:50424807-50430893) expressed in amnion with a high FPKM value of 7.1. Of note, this transcript is not documented in any human gene databases, although the existence of human expressed sequence tags (ESTs) at this locus further supports the validity of this TAR (Figure 8).


Transcriptome landscape of the human placenta.

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

An example of novel transcriptional active regions (TARs) identified in the present study. Shown is a novel TAR on chromosome 16 found in amnion. A wiggle plot of RNA-Seq read coverage, structures of 3 alternatively spliced transcripts and ESTs were shown from top to bottom. Note that there is no gene annotated in this region in the indicated annotation databases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: An example of novel transcriptional active regions (TARs) identified in the present study. Shown is a novel TAR on chromosome 16 found in amnion. A wiggle plot of RNA-Seq read coverage, structures of 3 alternatively spliced transcripts and ESTs were shown from top to bottom. Note that there is no gene annotated in this region in the indicated annotation databases.
Mentions: One major advantage of RNA-Seq compared to microarray technology is its capability to detect un-annotated novel transcripts. To identify novel transcriptional active regions (TARs) in placental tissues, we used the software Scripture [56] for ab initio reconstruction of transcripts for each tissue after sequence mapping with Tophat [21] (see details in Methods). We identified approximately 100,000 transcripts in each of the placental tissues with more than 70% of them being multi-exon transcripts (Table 2). To reduce false signals, only multiexon transcripts were used in the following analysis. After overlapping transcripts were merged into one single TAR, a total of 13,469, 16,987, and 15,158 TARs were found in amnion, chorion, and decidua, respectively. We filtered out the ones overlapping with the annotated transcripts from the NCBI RefSeq, UCSC, Ensembl, and Vega database and identified 604, 1,007, and 896 novel TARs in amnion, chorion, and decidua, respectively. The expression levels of the identified novel TARs are listed in Table S4 in Additional file 3. Importantly, a large proportion of these novel TARs (285, 456, and 468 in the corresponding placental tissues) are placenta-specific or more than 4 fold enriched compared to non-placental tissues. Shown in Figure 8 is one example of novel TARs on chromosome 16 (chr16:50424807-50430893) expressed in amnion with a high FPKM value of 7.1. Of note, this transcript is not documented in any human gene databases, although the existence of human expressed sequence tags (ESTs) at this locus further supports the validity of this TAR (Figure 8).

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