The faithful execution of molecular programme underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for efficient mammalian reproduction. However, the organization and principle of molecular circuits and modules for oocyte meiosis remain obscure. Here, we employed the recently developed single‐cell RNA‐seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non‐coding RNAs (lncRNAs) during oocyte in vitro meiotic maturation. During the transition from GV to MII, total number of detected RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1,807 (602 up‐ and 1,205 down‐regulated) mRNAs and 313 (177 up‐ and 136 down‐regulated) lncRNAs were significantly differentially expressed (DE), i.e., more mRNAs down‐regulated, but more lncRNAs up‐regulated. During maturation of pig oocytes, mitochondrial mRNAs were actively transcribed, eight of which (ND6, ND5, CYTB, ND1, ND2, COX1, COX2 and COX3) were significantly up‐regulated. Both DE mRNAs and targets of DE lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co‐expression network analysis (WGCNA) revealed 20 hub mRNAs in three modules to be important for oocyte meiosis and maturation. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in in vitro meiotic maturation of pig oocytes.
Excessive fat deposition can cause chicken health problem, and affect production efficiency by causing great economic losses to the industry. However, the molecular underpinnings of the complex adiposity trait remain elusive. In the current study, we constructed and compared the gene co-expression networks on four transcriptome profiling datasets, from two chicken lines under divergent selection for abdominal fat contents, in an attempt to dissect network compositions underlying adipose tissue growth and development. After functional enrichment analysis, nine network modules important to adipogenesis were discovered to be involved in lipid metabolism, PPAR and insulin signaling pathways, and contained hub genes related to adipogenesis, cell cycle, inflammation, and protein synthesis. Moreover, after additional functional annotation and network module comparisons, common sub-modules of similar functionality for chicken fat deposition were identified for different chicken lines, apart from modules specific to each chicken line. We further validated the lysosome pathway, and found TFEB and its downstream target genes showed similar expression patterns along with chicken preadipocyte differentiation. Our findings could provide novel insights into the genetic basis of complex adiposity traits, as well as human obesity and related metabolic diseases.
Maternal‐to‐zygotic transition (MZT) occurs when maternal transcripts decay and zygotic genome is activated gradually at the early stage of embryo development. Previously, single‐cell RNA‐seq (scRNA‐seq) has helped us to uncover the MZT‐associated mRNA dynamics of in vitro‐produced pig early embryos. Here, to further investigate functional modules and hub genes associated with MZT process, the weighted gene co‐expression network analysis (WGCNA) was performed on our previously generated 45 scRNA‐seq datasets. For the in vitro fertilized embryo (IVF) group, 5 significant modules were identified (midnight blue/black/red and blue/brown modules, positively correlated with 1‐cell (IVF1) and 8‐cell (IVF8), respectively), containing genes mainly enriched in signalling pathways such as Wnt, regulation of RNA transcription, fatty acid metabolic process, poly(A) RNA binding and lysosome. For the parthenogenetically activated embryo (PA) group, 9 significant modules were identified (black/purple/red, brown/turquoise/yellow, and magenta/blue/green modules, positively correlated with MII oocytes, 1‐cell (PA1) and 8‐cell (PA8), respectively), mainly enriched in extracellular exosome, poly(A) RNA binding, mitochondrion and transcription factor activity. Moreover, some of identified hub genes within 3 IVF and 9 PA significant modules, including ADCY2, DHX34, KDM4A, GDF10, ABCC10, PAFAH2, HEXIM2, COQ9, DCAF11, SGK1 and ESRRB, have been reported to play vital roles in different biological processes. Our findings provide information and resources for subsequent in‐depth study on the regulation and function of MZT in pig embryos.
Activator Protein 2 gamma (AP-2γ) is a master transcription factor that plays a critical role in the development and progression of breast cancer. However, the underlying mechanism is still unclear. Herein, using a proteomics approach, we identified Tripartite motif-containing 37 (TRIM37) as a novel coactivator of AP-2γ-mediated transcription in breast cancer cells. We demonstrate that TRIM37 facilitates AP-2γ chromatin binding to directly regulate the AP-2γ mediated transcriptional program. We also show that TRIM37 achieves this by stimulating K63 chain-linked ubiquitination of AP-2γ, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that the TRIM37-AP-2γ interaction is essential for breast cancer tumor growth. Overall, our work reveals that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.
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