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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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Analysis of placenta-enriched and -specific genes. (a) Number of tissue-enriched (blue bar) and tissue-specific (red bar) genes. Tissue-enriched genes were defined as genes with more than 4-fold change in expression and minimum FPKM of 1. (b) Proportions of overlapping genes between the placenta-enriched gene list and the MGI or PTB gene list (see text and Methods for details). The lighter shade indicates the proportion of non-placentaenriched genes while the darker shade indicates the proportion of placenta-enriched genes. P-values were determined by Fisher's exact test. (c) Expression profile of the 70 placenta-enriched MGI list genes. Gene expression values were normalized for each gene and color-coded using the same scheme depicted in Figure 1. (d) Expression patterns of placenta-specific genes in amnion, chorion, and decidua. Color scheme is based on log10(FPKM value).
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Figure 2: Analysis of placenta-enriched and -specific genes. (a) Number of tissue-enriched (blue bar) and tissue-specific (red bar) genes. Tissue-enriched genes were defined as genes with more than 4-fold change in expression and minimum FPKM of 1. (b) Proportions of overlapping genes between the placenta-enriched gene list and the MGI or PTB gene list (see text and Methods for details). The lighter shade indicates the proportion of non-placentaenriched genes while the darker shade indicates the proportion of placenta-enriched genes. P-values were determined by Fisher's exact test. (c) Expression profile of the 70 placenta-enriched MGI list genes. Gene expression values were normalized for each gene and color-coded using the same scheme depicted in Figure 1. (d) Expression patterns of placenta-specific genes in amnion, chorion, and decidua. Color scheme is based on log10(FPKM value).

Mentions: We identified 938, 865, and 944 genes with at least 4-fold enriched expression in amnion, chorion, and decidua, respectively, as compared to non-placental tissues, including 216 genes shared among the three compartments of the placenta. We also used a similar strategy to generate a list of 758 placenta-enriched genes using the GeneAtlas microarray data set covering whole placental and other human tissues [23] (see Methods for further details). Among the 758 array-based placenta-enriched genes, 297 were found to be enriched in one of the 3 placental tissues according to our RNA-Seq data, representing a significant overlap between the array and RNA-Seq results (p = 2.2e-119, Fisher's exact test). The difference between the array and RNA-Seq based gene lists could be due to the difference in platforms as well as in tissue samples used for expression profiling. We also used a similar approach to identify tissue-enriched genes in each of the 16 HBM2.0 tissues (15 other HBM2.0 tissues were used as the background). Of all 19 tissues, the three placental tissues were among the tissues with the highest number of tissue-enriched genes, with only testes, brain and white blood cells topping the placental tissues (Figure 2a).


Transcriptome landscape of the human placenta.

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

Analysis of placenta-enriched and -specific genes. (a) Number of tissue-enriched (blue bar) and tissue-specific (red bar) genes. Tissue-enriched genes were defined as genes with more than 4-fold change in expression and minimum FPKM of 1. (b) Proportions of overlapping genes between the placenta-enriched gene list and the MGI or PTB gene list (see text and Methods for details). The lighter shade indicates the proportion of non-placentaenriched genes while the darker shade indicates the proportion of placenta-enriched genes. P-values were determined by Fisher's exact test. (c) Expression profile of the 70 placenta-enriched MGI list genes. Gene expression values were normalized for each gene and color-coded using the same scheme depicted in Figure 1. (d) Expression patterns of placenta-specific genes in amnion, chorion, and decidua. Color scheme is based on log10(FPKM value).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Analysis of placenta-enriched and -specific genes. (a) Number of tissue-enriched (blue bar) and tissue-specific (red bar) genes. Tissue-enriched genes were defined as genes with more than 4-fold change in expression and minimum FPKM of 1. (b) Proportions of overlapping genes between the placenta-enriched gene list and the MGI or PTB gene list (see text and Methods for details). The lighter shade indicates the proportion of non-placentaenriched genes while the darker shade indicates the proportion of placenta-enriched genes. P-values were determined by Fisher's exact test. (c) Expression profile of the 70 placenta-enriched MGI list genes. Gene expression values were normalized for each gene and color-coded using the same scheme depicted in Figure 1. (d) Expression patterns of placenta-specific genes in amnion, chorion, and decidua. Color scheme is based on log10(FPKM value).
Mentions: We identified 938, 865, and 944 genes with at least 4-fold enriched expression in amnion, chorion, and decidua, respectively, as compared to non-placental tissues, including 216 genes shared among the three compartments of the placenta. We also used a similar strategy to generate a list of 758 placenta-enriched genes using the GeneAtlas microarray data set covering whole placental and other human tissues [23] (see Methods for further details). Among the 758 array-based placenta-enriched genes, 297 were found to be enriched in one of the 3 placental tissues according to our RNA-Seq data, representing a significant overlap between the array and RNA-Seq results (p = 2.2e-119, Fisher's exact test). The difference between the array and RNA-Seq based gene lists could be due to the difference in platforms as well as in tissue samples used for expression profiling. We also used a similar approach to identify tissue-enriched genes in each of the 16 HBM2.0 tissues (15 other HBM2.0 tissues were used as the background). Of all 19 tissues, the three placental tissues were among the tissues with the highest number of tissue-enriched genes, with only testes, brain and white blood cells topping the placental tissues (Figure 2a).

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