Dataset Information

RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation.

ABSTRACT: A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA-binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf??2bp2 (also commonly known as Imp2) in mouse embryos causes early embryonic developmental arrest in vitro at the 2-cell-stage. Transcriptomics and proteomics analyses of 2-cell-stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14, both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild-type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10-9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2-treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development-related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

SUBMITTER: Liu HB

PROVIDER: S-EPMC6685478 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation.

Liu Hong-Bin HB Muhammad Tahir T Guo Yueshuai Y Li Meng-Jing MJ Sha Qian-Qian QQ Zhang Chuan-Xin CX Liu Hui H Zhao Shi-Gang SG Zhao Han H Zhang Hao H Du Yan-Zhi YZ Sun Kang K Liu Kui K Lu Gang G Guo Xue-Jiang XJ Sha Jiahao J Fan Heng-Yu HY Gao Fei F Chen Zi-Jiang ZJ

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190524 15

A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA-binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of <i>Igf 2bp2</i> (also commonly known as <i>Imp2</i>) in mouse embryos causes early embryonic developmental arrest in vitro at the 2-cell-stage. Transcriptomics and proteomics analyses of 2-cell-stage embryos in mice reveal that deletion of IMP2 downregulates the expressi ...[more]

PMID: 31406667

Similar Datasets

Project description:High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. Tumor cells release extracellular vesicles (EVs) that can polarize macrophages towards tumor-associated macrophages (TAMs), which play a role in tumor progression. However, there is a lack of understanding of IMP2’s effect on TAMs. EVs were isolated from colorectal cancer HCT116 parental (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells via ultracentrifugation and tangential flow filtration. EVs were characterized according to MISEV guidelines and microRNA cargo was assessed by microRNA-Seq. Primary human monocyte-derived macrophages were polarized towards a TAM-like phenotype by EVs and the expression of genes and surface markers was assessed by qPCR and flow cytometry, respectively. Morphological changes of macrophages as well as the migratory potential of cancer cells were assessed by the IncuCyte® system and macrophage matrix degradation potential by zymography. Changes in the metabolic activity of macrophages were quantified in live cells in a Seahorse® analyzer. For in vivo studies, EVs were injected into the yolk sac of zebrafish embryos, and macrophages were isolated by fluorescence-activated cell sorting. EV samples from both WT and KO EVs had a similar size and concentration and were positive or CD9, CD81, CD63, and ALIX. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs, while the expression of tumor-suppressing TNF and IL6 was reduced. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. They exhibited a higher basal oxygen consumption rate and a lower extracellular acidification rate. microRNA-seq revealed a significant difference in the microRNA composition of WT and KO EVs. Macrophages transfected with miR-181a-5p mimic showed a lower level of the phosphatase DUSP6. Zebrafish macrophages upon polarization with WT EVs showed lower expression of IL6 and TNF. Our results show that IMP2 can determine the cargo of EVs released by cancer cells, thereby modulating the EVs’ actions on macrophages. Expression of IMP2 is responsible for the secretion of EVs that polarize macrophages toward a tumor-promoting phenotype.

Dataset Information

RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation.

Publications

RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets