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Dissecting the first transcriptional divergence during human embryonic development.

Bai Q, Assou S, Haouzi D, Ramirez JM, Monzo C, Becker F, Gerbal-Chaloin S, Hamamah S, De Vos J - Stem Cell Rev (2012)

Bottom Line: Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression.A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta.The induction of this network could be recapitulated in an in vitro trophoblast differentiation model.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1040, Montpellier, 34000, France.

ABSTRACT
The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model.

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Overview of TE expression profile and expression of cell cycle-specific genes in TE, hESCs, placenta and nervous system. a Unsupervised hierarchical clustering of the 181 panel samples. The first 30000 PS with the highest coefficient variation were analyzed with the Cluster software. Three cluster branches emerged: the nervous system branch (green), embryonic development and gamete branch (pink) and adult tissue branch (blue). b Proportion of genes from the cell cycle signature that are present in the TE, hESC, placenta and nervous system gene signatures
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Fig1: Overview of TE expression profile and expression of cell cycle-specific genes in TE, hESCs, placenta and nervous system. a Unsupervised hierarchical clustering of the 181 panel samples. The first 30000 PS with the highest coefficient variation were analyzed with the Cluster software. Three cluster branches emerged: the nervous system branch (green), embryonic development and gamete branch (pink) and adult tissue branch (blue). b Proportion of genes from the cell cycle signature that are present in the TE, hESC, placenta and nervous system gene signatures

Mentions: Mural TE was mechanically separated from the inner cell mass (ICM) of five fresh blastocyst stage (day 5) embryos produced by in vitro fertilization (IVF) and the five TE samples were then individually analyzed by whole genome Affymetrix oligonucleotide microarrays. Validation of the microarray data for three genes that were strongly up-regulated in the TE samples (DNMT3L, GAGE2 and GATA3) was performed by real-time quantitative PCR using five independent mural TE samples (Supplementary Figure S1). Unsupervised hierarchical clustering of the gene expression level data of the five TE samples and of a large panel that included hESC, germ cells, placenta and different adult tissue samples (n = 181) (see Materials and Methods and Supplementary Table S1) divided the samples in three main branches: a first one containing all the nervous system samples; a second one that included the TE, testis/oocytes, hESC, fibroblast and placenta samples, and a third branch containing all the other adult tissues (Fig. 1a). As expected, the TE samples clustered together with samples that were developmentally closer to them.Fig. 1


Dissecting the first transcriptional divergence during human embryonic development.

Bai Q, Assou S, Haouzi D, Ramirez JM, Monzo C, Becker F, Gerbal-Chaloin S, Hamamah S, De Vos J - Stem Cell Rev (2012)

Overview of TE expression profile and expression of cell cycle-specific genes in TE, hESCs, placenta and nervous system. a Unsupervised hierarchical clustering of the 181 panel samples. The first 30000 PS with the highest coefficient variation were analyzed with the Cluster software. Three cluster branches emerged: the nervous system branch (green), embryonic development and gamete branch (pink) and adult tissue branch (blue). b Proportion of genes from the cell cycle signature that are present in the TE, hESC, placenta and nervous system gene signatures
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285757&req=5

Fig1: Overview of TE expression profile and expression of cell cycle-specific genes in TE, hESCs, placenta and nervous system. a Unsupervised hierarchical clustering of the 181 panel samples. The first 30000 PS with the highest coefficient variation were analyzed with the Cluster software. Three cluster branches emerged: the nervous system branch (green), embryonic development and gamete branch (pink) and adult tissue branch (blue). b Proportion of genes from the cell cycle signature that are present in the TE, hESC, placenta and nervous system gene signatures
Mentions: Mural TE was mechanically separated from the inner cell mass (ICM) of five fresh blastocyst stage (day 5) embryos produced by in vitro fertilization (IVF) and the five TE samples were then individually analyzed by whole genome Affymetrix oligonucleotide microarrays. Validation of the microarray data for three genes that were strongly up-regulated in the TE samples (DNMT3L, GAGE2 and GATA3) was performed by real-time quantitative PCR using five independent mural TE samples (Supplementary Figure S1). Unsupervised hierarchical clustering of the gene expression level data of the five TE samples and of a large panel that included hESC, germ cells, placenta and different adult tissue samples (n = 181) (see Materials and Methods and Supplementary Table S1) divided the samples in three main branches: a first one containing all the nervous system samples; a second one that included the TE, testis/oocytes, hESC, fibroblast and placenta samples, and a third branch containing all the other adult tissues (Fig. 1a). As expected, the TE samples clustered together with samples that were developmentally closer to them.Fig. 1

Bottom Line: Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression.A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta.The induction of this network could be recapitulated in an in vitro trophoblast differentiation model.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1040, Montpellier, 34000, France.

ABSTRACT
The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model.

Show MeSH
Related in: MedlinePlus