The accessible chromatin landscape during conversion of human embryonic stem cells to trophoblast by bone morphogenetic protein 4†

Li, Yajun; Ding, Dewu; Liu, Hongde; Sun, Xiao

doi:10.1093/biolre/iox028

Cited by 13 publications

(16 citation statements)

References 94 publications

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“…Finally, when we compared ESCd to three commonly used placental cell lines: HTR-8/SVneo, BeWo, and JEG-3, we found that genes upregulated in ESCd were enriched for terms associated with cell invasion. These results provide strong evidence that after BAP treatment hESC differentiate into a subset of invasive placental cells, and may provide good model for studying TB functions, including invasion, as has been demonstrated in a number of other studies 40 – 44 .…”

Section: Discussionsupporting

confidence: 77%

Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate

Jain

Ezashi

Roberts

et al. 2017

Sci Rep

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Differentiated human embryonic stem cells (hESC) continue to provide a model for studying early trophoblast cells (TB), but many questions have been raised regarding their true identity. Therefore, we carried out a global and unbiased analysis on previously published transcriptomic profiles for hESC differentiated to TB by means of bone morphogenetic protein-4 and inhibitors of activin A and fibroblast growth factor-2 signaling (BAP treatment). Our results confirm that BAP treated hESC (ESCd) lack a mesoderm signature and are a subtype of placental cells unlike those present at term. ESCd display a high level of expression of genes implicated in migration and invasion compared to commonly used, immortalized TB cell lines and primary cells from term placenta. Co-expression network analysis also identified gene modules involved in cell migration and adhesion, processes that are likely critical during the beginning stages of placentation. Finally, protein-protein interaction analysis predicted several additional genes that may play important roles in early stages of placental development. Together, our analyses provide novel insights into the transcriptional programs that are active in ESCd.

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Section: Discussionsupporting

confidence: 77%

Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate

Jain

Ezashi

Roberts

et al. 2017

Sci Rep

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“…Some key transcription factors (TFs) affecting differentiation have been identified, such as POU5F1, SOX2, and KLF4 (Nichols et al, 1998;Takahashi and Yamanaka, 2006;Goolam et al, 2016). Previously, our lab identified TFs for DNase I hypersensitive sites based on public available chromatin accessibility data of human embryonic stem cells (ESCs) and BMP4-induced trophoblast cell lines (Liu et al, 2017). The chromatin structure, including nucleosome positions, DNA methylation, and histone modifications also changed during the differentiation (Su et al, 2012;Xie et al, 2013;de Boni et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Since Xu et al proved that bone morphogenetic protein 4 (BMP4) could induce human ESCs, efficiently differentiating to trophoblast lineage, multiple research institutes have adopted this system as a model to study trophoblast lineage specification in vitro (Xu et al, 2002). Roberts's et al considered this model reliability by analyzing gene expression profiling through RNA sequencing (RNA-Seq) technology (Yabe et al, 2016;Liu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast

Liu

et al. 2020

Front. Genet.

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The role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nucleotide variations and ∼4,500 indels by comparing the genome sequenced data between the stem cell lines and the matched BMP4induced trophoblast cell lines and annotated them by integrating the epigenomic and transcriptomic datasets. Relatively, introns enrich more variations. We found ∼45% (42 genes) of the differentially expressed genes in trophoblasts that associate genomic variations. Six variations, located at transcription factor binding sites where H3K4me3 and H3K27ac are enriched in both H1 and H1_BMP4, were identified. The epigenetic status around the genomic variations in H1 was similar to that in H1_BMP4. This means that the variation-associated gene's expression change can not be attributed to epigenetic alteration. The genes associated with the six variations were upregulated in differentiation. We inferred that during the differentiation, an increased in the expression level of the MEF2C gene is due to a genomic variation in chromosomes 5: 88179358 A > G, which is at a binding site of TFs KLF16, NR2C2, and ZNF740 to MEF2C. Allele G shows a higher affinity to the TFs in the induced cells. The increased expression of MEF2C leads to an increased expression of TF MEF2C's target genes, subsequently affecting the differentiation. Although genomic variation should not be a dominant factor in differentiation, we believe that genomic variation could indeed play a role in the differentiation from stem cells into trophoblast.

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“…Utilizing a dataset from the Roadmap project, Liu et al [31] studied the DNase-seq landscape of BMP4-treated hESCs to identify cis-elements regulating early placental development. Though previously debated [32], recent evidence suggests that BMP4-treated hESCs represent early invasive trophoblast cells [33][34][35].…”

Section: Genome-wide Identification Of Enhancer Elements In the Humanmentioning

confidence: 99%

Genome-wide identification of enhancer elements in the placenta

2019

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Normal placental development is essential for a healthy pregnancy, and is contingent upon tight spatiotemporal regulation of gene expression. One level of transcriptional control is via enhancer elements in the genome. Enhancers are distal cis-regulatory elements that can impact gene expression regardless of their position or orientation. The study of enhancers in the placenta is usually focused on one or two at a time, and the simultaneous identification of all enhancers has been limited. However, such a holistic approach is necessary if we are to gain a systems-level understanding of gene expression regulation in the placenta. Here, we review current methods for genome-scale enhancer identification, as well as studies that have applied those techniques in the placenta, with the aim of guiding future research.

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The accessible chromatin landscape during conversion of human embryonic stem cells to trophoblast by bone morphogenetic protein 4†

Cited by 13 publications

References 94 publications

Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate

Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate

Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast

Genome-wide identification of enhancer elements in the placenta

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