Surface Lin28A Expression Consistent With Cellular Stress Parallels Indicators of Senescence
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ABSTRACT:
PROVIDER: PRJNA772780 | ENA |
REPOSITORIES: ENA
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Project description:AimsDeclining cellular functional capacity resulting from stress or ageing is a primary contributor to impairment of myocardial performance. Molecular pathway regulation of biological processes in cardiac interstitial cells (CICs) is pivotal in stress and ageing responses. Altered localization of the RNA-binding protein Lin28A has been reported in response to environmental stress, but the role of Lin28A in response to stress in CICs has not been explored. Surface Lin28A redistribution is indicative of stress response in CIC associated with ageing and senescence.Methods and resultsLocalization of Lin28A was assessed by multiple experimental analyses and treatment conditions and correlated to oxidative stress, senescence, and ploidy in adult murine CICs. Surface Lin28A expression is present on 5% of fresh CICs and maintained through Passage 2, increasing to 21% in hyperoxic conditions but lowered to 14% in physiologic normoxia. Surface Lin28A is coincident with elevated senescence marker p16 and beta-galactosidase (β-gal) expression in CICs expanded in hyperoxia, and also increases with polyploidization and binucleation of CICs regardless of oxygen culture. Transcriptional profiling of CICs using single-cell RNA-Seq reveals up-regulation of pathways associated with oxidative stress in CICs exhibiting surface Lin28A. Induction of surface Lin28A by oxidative stress is blunted by treatment of cells with the antioxidant Trolox in a dose-dependent manner, with 300 μM Trolox exposure maintaining characteristics of freshly isolated CICs possessing low expression of surface Lin28A and β-gal with predominantly diploid content.ConclusionSurface Lin28A is a marker of environmental oxidative stress in CICs and antioxidant treatment antagonizes this phenotype. The biological significance of Lin28 surface expression and consequences for myocardial responses may provide important insights regarding mitigation of cardiac stress and ageing.
| S-EPMC10409908 | biostudies-literature
Project description:Single-cell RNA-seq (10X Genomics Chromium) to profile Adult cardiac interstitial sorted based on the presence of Lin28 on cell membrane surface Lin28S+/-.
2021-10-22 | GSE186176 | GEO
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, Lin28 was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28A preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of RNA binding of LIN28A and translation in mouse embryonic stem cell.
2012-10-25 | E-GEOD-37111 | biostudies-arrayexpress
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of miRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a
2012-10-25 | E-GEOD-37112 | biostudies-arrayexpress
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of mRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a
2012-10-25 | E-GEOD-37113 | biostudies-arrayexpress
Project description:We report the upregulated genes by the expression of LIN28A or loss of function mutant of LIN28A for 293FTcells..
2023-01-11 | GSE174387 | GEO
Project description:We report the direct target genes by LIN28A or loss of function mutant of LIN28A for 293FTcells using CLIP-Seq
2023-01-11 | GSE174388 | GEO
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells.
2012-10-25 | GSE37112 | GEO
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, Lin28 was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28A preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells.
2012-10-25 | GSE37111 | GEO
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells.
2012-10-25 | GSE37113 | GEO