Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells

Lee, Bumkyu; Jang, Yu Jin; Kim, Mijeong; LeBlanc, Lucy; Rhee, Catherine; Lee, Jiwoon; Beck, Samuel J.; Shen, Wenwen; Kim, Jonghwan

doi:10.1038/s41467-019-12720-6

Cited by 52 publications

(68 citation statements)

References 67 publications

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“…Abnormalities in circRNA expression play important roles in tumorigenesis and development. Recent research study demonstrated that circ-DICER1 regulated proliferation, migration and tube formation of GECs through targeting MOV10 [34]. Accordingly, we screened out the cir-cRNAs which were regulated by SRSF10 in GECs, and finally focused on circ-ATXN1.…”

Section: Discussionmentioning

confidence: 99%

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

Liu

Shen

Zhu

et al. 2020

J Exp Clin Cancer Res

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Background: Angiogenesis plays an important role in the progress of glioma. RNA-binding proteins (RBPs) and circular RNAs (circRNAs), dysregulated in various tumors, have been verified to mediate diverse biological behaviors including angiogenesis. Methods: Quantitative real-time PCR (qRT-PCR) and western blot were performed to detect the expression of SRSF10, circ-ATXN1, miR-526b-3p, and MMP2/VEGFA. The potential function of SRSF10/circ-ATXN1/miR-526b-3p axis in glioma-associated endothelial cells (GECs) angiogenesis was further studied. Results: SRSF10 and circ-ATXN1 were significantly upregulated in GECs compared with astrocyte-associated endothelial cells (AECs). Knockdown of SRSF10 or circ-ATXN1 significantly inhibited cell viability, migration and tube formation of GECs where knockdown of SRSF10 exerted its function by inhibiting the formation of circ-ATXN1. Moreover, the combined knockdown of SRSF10 and circ-ATXN1 significantly enhanced the inhibitory effects on cell viability, migration and tube formation of GECs, compared with knockdown of SRSF10 and circ-ATXN1, respectively. MiR-526b-3p was downregulated in GECs. Circ-ATXN1 functionally targeted miR-526b-3p in an RNA-induced silencing complex. Up-regulation of miR-526b-3p inhibited cell viability, migration and tube formation of GECs. Furthermore, miR-526b-3p affected the angiogenesis of GECs via negatively regulating the expression of MMP2/ VEGFA. Conclusion: SRSF10/circ-ATXN1/miR-526b-3p axis played a crucial role in regulating the angiogenesis of GECs. The above findings provided new targets for anti-angiogenic therapy in glioma.

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Section: Discussionmentioning

confidence: 99%

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

Liu

Shen

Zhu

et al. 2020

J Exp Clin Cancer Res

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“…8A-C) . While clusters 1,2,3 are enriched for binding motifs of the GETM reprogramming factors Gata3, Tfap2c and Eomes as well as Tbx6 and FOS/Atf3/AP-1, cluster 4 is enriched for binding motifs for AP-1 and for the master TSC regulator, TEAD 68 . Moreover, while clusters 1,2,3 contain mostly intronic and intergenic ATAC-seq peaks, cluster 4 encompasses a large fraction of transcription start site (TSS) ATAC-seq peaks.…”

Section: Resultsmentioning

confidence: 99%

Comparative Parallel Multi-Omics Analysis During the Induction of Pluripotent and Trophectoderm States

Jaber¹,

Radwan²,

Loyfer

et al. 2020

Preprint

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Following fertilization, totipotent cells divide to generate two compartments in the early embryo: the inner cell mass (ICM) and trophectoderm (TE). It is only at the 32-64 -cell stage when a clear segregation between the two cell-types is observed, suggesting a T-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro by nuclear reprogramming share similar dynamics/trajectories. We conducted a comparative parallel multi-omics analysis on cells undergoing reprogramming to Induced pluripotent stem cells (iPSCs) and induced trophoblast stem cells (TSCs), and examined their transcriptome, methylome, chromatin accessibility and activity and genomic stability. Our analysis revealed that cells undergoing reprogramming to pluripotency and TSC state exhibit specific trajectories from the onset of the process, suggesting V-shaped model. Using these analyses, not only we could describe in detail the various trajectories toward the two states, we also identified previously unknown stage-specific reprogramming markers as well as markers for faithful reprogramming and reprogramming blockers. Finally, we show that while the acquisition of the TSC state involves the silencing of embryonic programs by DNA methylation, during the acquisition of pluripotency these specific regions are initially open but then retain inactive by the elimination of the histone mark, H3K27ac.

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“…EP300 has been described to potentiate SOX9-dependent transcription 71 and Sox9 -deficient intestinal epithelium fails to mature 72 . Mapping of EP300-binding sites was recently utilized to identify transcriptional networks in specialized cell types in the placenta 73 , inspiring further investigation of epigenetic modifier-aided transcription in different IEC lineages. To summarize, we developed a resource that allows to compare the requirement of various epigenetic modifiers for intestinal epithelial renewal and IEC differentiation.…”

Section: Discussionmentioning

confidence: 99%

A semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation

Ostrop

Zwiggelaar

Pedersen

et al. 2020

Preprint

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The intestinal epithelium maintains an important barrier throughout life. It consists of several epithelial cell lineages that are derived from LGR5+ intestinal stem cells. Although epigenetic regulation of embryonic stem cell differentiation is well established, its role in adult stem cell systems such as the intestinal epithelium is still undefined. Yet, targeting of epigenetic regulatory enzymes may be relevant for new therapeutics, for example in cancer treatment. Here, we combine a newly established organoid toolbox with an epigenetic probe library to identify epigenetic regulators of intestinal epithelial biology. We discover several probes that alter intestinal epithelial biology including those targeting HDACs, EP300/CREBBP, LSD1, and type I PRMTs. We conclude that epigenetic modifiers are primarily involved in mediating maturation of the epithelium rather than dictating specific cell lineage differentiation. Furthermore, we show that inhibiting type I PRMTs, which leads to epithelial maturation, blocks the growth of adenoma but not normal organoid cultures. Thus, epigenetic probes are a powerful tool in defining biological processes and demonstrate therapeutic potential.

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Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells

Cited by 52 publications

References 67 publications

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

Comparative Parallel Multi-Omics Analysis During the Induction of Pluripotent and Trophectoderm States

A semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation

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