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Integrin ?2 marks a niche of trophoblast progenitor cells in first trimester human placenta.

ABSTRACT: During pregnancy the trophoblast cells of the placenta are the only fetal cells in direct contact with maternal blood and decidua. Their functions include transport of nutrients and oxygen, secretion of pregnancy hormones, remodelling of the uterine arteries, and communicating with maternal cells. Despite the importance of trophoblast cells in placental development and successful pregnancy, little is known about the identity, location and differentiation of human trophoblast progenitors. We identify a proliferative trophoblast niche at the base of the cytotrophoblast cell columns in first trimester placentas that is characterised by integrin ?2 (ITGA2) expression. Pulse-chase experiments with 5-iodo-2'-deoxyuridine indicate that these cells might contribute to both villous (VCT) and extravillous (EVT) lineages. These proliferating trophoblast cells can be isolated by flow cytometry using ITGA2 as a marker and express genes from both VCT and EVT. Microarray expression analysis shows that ITAG2+ cells display a unique transcriptional signature, including genes involved in NOTCH signalling, and exhibit a combination of epithelial and mesenchymal characteristics. ITGA2 thus marks a niche allowing the study of pure populations of trophoblast progenitor cells.

SUBMITTER: Lee CQE

PROVIDER: S-EPMC6124543 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta.

Lee Cheryl Q E CQE Turco Margherita Y MY Gardner Lucy L Simons Benjamin D BD Hemberger Myriam M Moffett Ashley A

Development (Cambridge, England) 20180416 16

During pregnancy the trophoblast cells of the placenta are the only fetal cells in direct contact with maternal blood and decidua. Their functions include transport of nutrients and oxygen, secretion of pregnancy hormones, remodelling of the uterine arteries, and communicating with maternal cells. Despite the importance of trophoblast cells in placental development and successful pregnancy, little is known about the identity, location and differentiation of human trophoblast progenitors. We iden ...[more]

PMID: 29540503

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Project description:BACKGROUND:Development of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood. METHODS:RNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth. RESULTS:RNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation. CONCLUSIONS:This study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.

Dataset Information

Integrin ?2 marks a niche of trophoblast progenitor cells in first trimester human placenta.

Publications

Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta.

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