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: Not available
| S-EPMC10293758 | biostudies-literature
Project description:The transition of embryonic stem cells (ESCs) from pluripotency to lineage commitment involves complex regulatory mechanisms, including chromatin dynamics and transcriptional/post- transcriptional processes. These mechanisms often interact within intricate networks that require thorough investigation. In this study, we highlight the critical role of the mouse RNA-binding protein LIN28A in neuronal differentiation. LIN28A mediates RNA-dependent interactions with thePolycomb repressive complex 2 (PRC2), leading to the eviction of PRC2 from chromatin andactivation of a neuronal lineage-specific transcriptional program. Proteomic analyses revealed thatthe LIN28A interactome undergoes substantial remodeling during differentiation, corresponding to changes in LIN28A localization. In undifferentiated ESCs, LIN28A primarily resides in the nucleus,interacting with PRC2 components in an RNA-dependent manner, assisting in chromatin dynamics. The absence of LIN28A results in persistent PRC2 association with chromatin, impairing theexpression of genes critical for neuronal differentiation. Chromatin immunoprecipitationsequencing further confirmed that loss of LIN28A results in preferential PRC2 occupancy at thepromoters of differentiation-associated genes. These findings reveal a novel role of LIN28A inepigenetic remodeling, crucial for proper neuronal differentiation of ESCs.
2026-05-01 | GSE306869 | GEO
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:LIN28a is an RNA binding protein that was initially characterized for its role in the negative regulation of let-7 microRNA biogenesis. In the last years a new role in the regulation of mRNA translation has been highlighted. This mechanism seems to be particularly relevant in the exit of embryonic stem cells (ESCs) from the naïve state and in the first phases of differentiation process. We have demonstrated that in the first step of ESC differentiation, i.e. the establishment of epiblast-like-cells and the formation of neural precursors, LIN28a enhances the translation of de novo DNA methyltransferase Dnmt3a [1] and blocks that of the chromatin architectural factor Hmga2 [2]. How LIN28a fulfils these opposite functions in ESC differentiation is still unknown. Our preliminary results indicated that LIN28a contributes in several ways to guide ESC differentiation possibly by changing molecular partners and regulating different targets. To explore this idea, we have generated Lin28a KO ESCs using CRISPR-Cas9 technology to study how Lin28a contributes to ESC differentiation. We have found that Lin28a KO ESCs are not able to properly exit from the naïve state to undergo a differentiation program. This effect seems to be due to the impairment of different cellular processes. To better characterize this role in ESC fate we have analyzed the molecular interactions of LIN28a at different steps of ESC differentiation through proteomics approaches. Moreover, to identify the direct mRNA targets of LIN28a we are developing an iCLIP protocol suitable to analyze the binding of LIN28a to RNAs during ESC differentiation. These data coupled with the phenotypic and proteomics analysis will contribute to understand the emerging fundamental role of RNA binding proteins in differentiation and development.
2026-05-05 | PXD049332 | Pride
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
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:During the early stages of embryonic development, Lin28a is expressed at high levels and gradually decreases as the embryo develops. As an RNA-binding protein, Lin28a maintains a subset of adult muscle stem cells (MuSCs) in an embryonic-like state. However, the specific mechanism for regulating RNA metabolism is not yet clear. Through the analysis of Lin28a-associated genes, we have revealed that Lin28a promotes the expression of Igf2bp3 and interacts with the Igf2bp3 protein, controlling the proliferation of MuSCs. In response to stress stimuli, Lin28a rapidly upregulates the expression of Igf2bp3, recruits mRNAs by interacting with the N6-methyladenosine (m6A) reader Igf2bp3, and forms protein complexes with G3bp1 in stress granules. Sequencing of the transcriptome and RNAs immunoprecipitated by Lin28a, Igf2bp3, and m6A antibodies in Lin28a+ MuSCs further revealed that Lin28a and Igf2bp3 collaboratively regulate the expression of DNA repair-related genes such as Fancm and Usp1 to promote DNA repair after oxidative stress. Therefore, Lin28a regulates the expression of DNA damage repair-related genes and upregulates the DNA stress response of MuSCs through stress granule regulation of m6A-modified mRNAs. This positive regulation contributes to the self-renewal of MuSCs.
2024-12-18 | GSE262720 | 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:We report the upregulated genes by the expression of LIN28A or loss of function mutant of LIN28A for 293FTcells..
2023-01-11 | GSE174387 | GEO