Effect of 30Kc19α-Lin28A protein on gene expression in osteogenesis of urine-derived stem cells
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ABSTRACT:
PROVIDER: PRJNA976235 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24737981.fastq.gz | Fastqsanger.gz | |||
| SRR24737982.fastq.gz | Fastqsanger.gz | |||
| SRR24737983.fastq.gz | Fastqsanger.gz |
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Project description:To elucidate the function of 30Kc19α-Lin28A protein in osteogenic differentiation of urine-derived stem cells, we established urine-derived stem cell lines differentiated with or without protein treatment. We then performed gene expression profiling analysis using data obtained from RNA-seq of osteogenic differentiated urine-derived stem cells with or without 30Kc19α-Lin28A protein treatment, undifferentiated urine-derived stem cells, and human osteoblasts
2023-06-01 | GSE233420 | GEO
Project description:Urine-derived stem cells (USCs) are a promising source for regenerative medicine because of their advantages such as easy and non-invasive collection from the human body, stable expansion, and the potential to differentiate into multiple lineages, including osteoblasts. In this study, we propose a strategy to enhance the osteogenic potential of human USCs using Lin28A, a transcription factor that inhibits let-7 miRNA processing. To address concerns regarding the safety of foreign gene integration and potential risk of tumorigenicity, we intracellularly delivered Lin28A as a recombinant protein fused with a cell-penetrating and protein-stabilizing protein, 30Kc19α. 30Kc19α–Lin28A fusion protein exhibited improved thermal stability and was delivered into USCs without significant cytotoxicity. 30Kc19α–Lin28A treatment elevated calcium deposition and upregulated several osteoblast-specific gene expressions in USCs derived from multiple donors. Our results indicate that intracellularly delivered 30Kc19α–Lin28A enhances the osteoblastic differentiation of human USCs by affecting the transcriptional regulatory network involved in metabolic reprogramming and stem cell potency. Therefore, 30Kc19α–Lin28A may provide a technical advancement toward developing clinically feasible strategies for bone regeneration.
| S-EPMC10293758 | biostudies-literature
Project description:A developmentally regulated RNA binding protein, LIN28A and its homolog LIN28B may share a similar mechanism to regulate the processing of let-7 microRNAs (miRNAs) in embryonic stem cells (ESCs) or certain cancer cells, although their predominant localization is different in cells. However, little is known about the regulatory mechanism of LIN28A for miRNA processing in the nucleus. Here, we show that SET7/9, a known histone methyltransferase, associates with LIN28A in vivo and in vitro. SET7/9-mediated methylation significantly leads to the nuclear retention and protein stability of LIN28A, and remarkably regulated RNA binding ability of LIN28A to pri-let-7. Using RNAi knockdown approach, we find that the methylated nuclear form of LIN28A may function in the nucleoli by sequestering the primary let-7 miRNA to block their processing through a Tut4 (Zcchc11)-independent mechanism to regulate human ESC pluripotency. We propose a new insight toward the understanding of the molecular mechanism for post-translational methylation of nuclear LIN28A along modulating pluripotency by regulating pri-let-7 miRNAs in human ESCs.
2016-12-05 | GSE53038 | GEO
Project description:Lin28, a well-known RNA-binding protein, regulates diverse cellular properties. All physiological functions of Lin28A characterized so far have been attributed to its repression of let-7 miRNA biogenesis or modulation of the mRNA translational efficiency. Here we show that Lin28A directly binds to a consensus DNA sequence in vitro and in mouse embryonic stem cells in vivo. ChIP-seq and RNA-seq reveal the enrichment of Lin28A binding around transcription start sites, and a positive correlation between its genomic occupancy and expression of many associated genes. Mechanistically, Lin28A recruits 5-methylcytosine-dioxygenase Tet1 to genomic binding sites to orchestrate 5-methylcytosine and 5-hydroxymethylcytosine dynamics. Either Lin28A or Tet1 knockdown leads to dysregulated DNA methylation and expression of common target genes. These results reveal a surprising role for Lin28A in transcriptional regulation via epigenetic DNA modifications and provide a new framework for understanding mechanisms underlying versatile functions of Lin28A in mammalian systems. Examine the DNA binding ability of Lin28 and its roles in regulating gene expression by coordinating with Tet1
2015-12-07 | E-GEOD-74254 | biostudies-arrayexpress
Project description:The RNA-binding protein LIN28A is required for maintaining tissue homeostasis, including in the reproductive system, but the underlying mechanisms on how LIN28A regulates germline progenitors remain unclear. Here, we dissected LIN28A-binding targets using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse testes. LIN28A preferentially binds to mRNA coding sequence (CDS) or 3'UTR regions at sites enriched wiGAG(A) sequences. Further investigation of Lin28a null mouse testes indicated that meiosis-associated mRNAs bound by LIN28A were differentially expressed. Next, ribosome profiling revealed that the mRNA levels of these targets were significantly reduced in polysome fractions, and their protein expression levels decreased in the Lin28a null mouse testes, even when meiotic arrest in the null mouse testes was not apparent. Collectively, these findings provide a set of LIN28A-regulated target mRNAs, and show that LIN28A binding might be mechanism through which LIN28A acts to regulate undifferentiated spermatogonia fates and male fertility in mammals.
2020-06-08 | GSE134033 | GEO
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. 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, 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:A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPC). We profiled the endogenous LIN28A-interacting proteins in NPC differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.
| MSV000084371 | MassIVE