The placenta is essential for sustaining the growth of the fetus during gestation. Defects in the functioning of the organ can result in a vast array of serious disorders and conditions, including chronic and acute fetal hypoxia, deteriorated fetal well-being, intrauterine growth restriction (IUGR), or even fetal mortality. Consonant expression of crucial genes is required for the proper functioning of the placenta [1]. Spatiotemporal expression is a huge impediment in any transcriptome analysis, especially in the placenta, an organ that constantly adapts to feto-maternal environmental alterations. Nevertheless, ribonucleic acid
The aim of the current paper was to provide a brief overview of recent advances in the human placental transcriptome, together with the immediate implications of these findings. New technologies stand behind the new quality of results.
Recent studies using massive parallel sequencing techniques greatly contributed to the expansion of our knowledge on the placenta! transcriptional landscape in various eutherians: elephants, rats, pigs, beavers, and humans [3, 4, 5, 6]. Research specifically focused on global analysis of human placenta transcriptome using RNA-seq and bioinformatics tools to identify the profile of the gene expression and characterization of transcripts involved in the regulation of molecular mechanisms in late (36-41 weeks) single and twin uncomplicated human pregnancies, and important aspects of the placenta! functioning were introduced. Among the 228,044 identified transcripts, expression values were calculated for all the 38,948 transcriptional active regions (TARs). Within the TARs, there were 9,434 previously unknown regions that may play a specific role in the functioning of the placenta were identified and described.
Analyses revealed
The processes of AS generate a variety of transcripts and, hence, the formation of multiple isoforms of a single protein. This mechanism can substantially modulate the functions of genes influencing the development of various diseases [11]. The reduced level of the PAPPA complex is associated with abnormalities that may result in IUGR, premature delivery, miscarriage, and preeclampsia [12]. New transcripts and splicing forms provide new information on the expression profile in the human placenta during normal pregnancy, which may be investigated as potentially useful in clinical genomics.
Other studies concentrated on the thorough analyses of the placenta transcriptome, including those of long non-coding RNA (IncRNA), an important genomic element that modulates gene signaling pathways [5]. Analysis of the expression level revealed 5 IncRNA loci and 21 coding genes that were differentially expressed depending on the sex of the fetus. Of the IncRNAs,
Changes were detected both in the exon expression and splicing sites in the
The results of the whole placental transcriptome sequencing established the foundations for the analyses of particular genes and enabled the identification of 1,364 bp of cDNA in human pregnancy-associated glycoprotein, also known as hPAG-L/pep [4].
Another approach in transcriptomics that was recently presented aimed to characterize the expression profile in placentas from pregnancies complicated by IUGR [6]. The use of restrictive bioinformatics algorithms allowed the identification of 37,501 TARs and the selection of 28 differentially expressed genes in IUGR samples. Functional analysis showed that most differentially expressed genes
Additionally, changes that may be associated with the regulation of isoform expression and production of functional proteins were detected in
Alignment of RNA-seq reads to the human genome revealed 88,859 potential single nucleotide variant sites. Functional analysis of genes with detected nonsynonymous single nucleotide variant sites
Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes identified in lUGR-affected placentas. Adapted from [6].
ID | Term | Gene |
---|---|---|
antigen receptor-mediated signaling pathway | ITK, ZAP70, TESPA1, THEMIS, LCK | |
T-cell receptor signaling pathway | ITK, ZAP70, TESPA1, THEMIS, LCK | |
leukocyte cell-cell adhesion | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
regulation of leukocyte cell-cell adhesion | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
leukocyte activation | SIRPG, ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
lymphocyte activation | SIRPG, ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
T-cell activation | SIRPG, ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
immune system development | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK, LTB | |
hematopoietic or lymphoid organ development | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK, LTB | |
hemopoiesis | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK, | |
positive regulation of cell-cell adhesion | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
positive regulation of leukocyte cell-cell adhesion | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
regulation of T-cell activation | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
leukocyte differentiation | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
lymphocyte differentiation | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
T-cell differentiation | ITK, ZAP70, BCL11B, TESPA1, IL7R, THEMIS, LCK | |
T-cell selection | ZAP70, BCL11B, THEMIS | |
positive Cell selection | ZAP70, BCL11B, THEMIS | |
T-cell differentiation in thymus | ZAP70, BCL11B, TESPA1, IL7R | |
positive regulation of lymphocyte activation | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
positive regulation of T-cell activation | SIRPG, ZAP70, TESPA1, IL7R, LCK | |
non-membrane spanning protein tyrosine kinase activity | ITK, ZAP70, LCK | |
NF-kappa B signaling pathway | ZAP70, LCK, LTB | |
T-cell receptor signaling pathway | ITK, ZAP70, LCK | |
Primary immunodeficiency | ZAP70, IL7R, LCK |
The recent progress in human placental transcriptomics provided data regarding the identification and global analysis of: transcriptome, expression of non-coding sequences, new gene variants and isoforms, and the mechanisms and effects of alternative splicing. The characterization of genes expressed in the placenta and their products may be the basis for the identification of molecular mechanisms determining effective reproduction. The following step in our understanding of distinctions between the normal and complicated pregnancy is to investigate the potentially crucial genes that were indicated together with mechanisms standing behind them