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ESCs lncrna

Jiajie Tu, Geng Tian, Hoi-Hung Cheung, Wei Wei, Tin-Lap Lee
BACKGROUND: The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). METHODS: In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR...
March 21, 2018: Stem Cell Research & Therapy
Buqing Ye, Benyu Liu, Liuliu Yang, Xiaoxiao Zhu, Dongdong Zhang, Wei Wu, Pingping Zhu, Yanying Wang, Shuo Wang, Pengyan Xia, Ying Du, Shu Meng, Guanling Huang, Jiayi Wu, Runsheng Chen, Yong Tian, Zusen Fan
Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that lncKdm2b , a divergent lncRNA for Kdm2b gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. LncKdm2b knockout impairs ESC self-renewal and causes early embryonic lethality. LncKdm2b can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex in trans Zbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner...
April 13, 2018: EMBO Journal
Alessandro Fiorenzano, Emilia Pascale, Miriam Gagliardi, Sara Terreri, Mariarosaria Papa, Gennaro Andolfi, Marco Galasso, Guidantonio Malagoli Tagliazucchi, Cristian Taccioli, Eduardo Jorge Patriarca, Amelia Cimmino, Maria Rosaria Matarazzo, Gabriella Minchiotti, Annalisa Fico
Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics...
March 13, 2018: Stem Cell Reports
Maria Winzi, Nuria Casas Vila, Maciej Paszkowski-Rogacz, Li Ding, Svenja Noack, Mirko Theis, Falk Butter, Frank Buchholz
RNA interference (RNAi) screens have been shown to be valuable to study embryonic stem cell (ESC) self-renewal and they have been successfully applied to identify coding as well as noncoding genes required for maintaining pluripotency. Here, we used an RNAi library targeting >640 long noncoding RNAs (lncRNA) to probe for their role in early cell differentiation. Utilizing a Sox1-GFP ESC reporter cell line, we identified the lncRNA lncR492 as lineage-specific inhibitor of neuroectodermal differentiation. Molecular characterization showed that lncR492 interacts with the mRNA binding protein HuR and facilitates its inhibitory function by activation of Wnt signaling...
2018: PloS One
Tobias C Messemaker, Selina M van Leeuwen, Patrick R van den Berg, Anke E J 't Jong, Robert-Jan Palstra, Rob C Hoeben, Stefan Semrau, Harald M M Mikkers
The transcription factor Sox2 controls the fate of pluripotent stem cells and neural stem cells. This gatekeeper function requires well-regulated Sox2 levels. We postulated that Sox2 regulation is partially controlled by the Sox2 overlapping long non-coding RNA (lncRNA) gene Sox2ot. Here we show that the RNA levels of Sox2ot and Sox2 are inversely correlated during neural differentiation of mouse embryonic stem cells (ESCs). Through allele-specific enhanced transcription of Sox2ot in mouse Sox2eGFP knockin ESCs we demonstrate that increased Sox2ot transcriptional activity reduces Sox2 RNA levels in an allele-specific manner...
January 10, 2018: Scientific Reports
Qiuli Fu, Zhenwei Qin, Lifang Zhang, Danni Lyu, Qiaomei Tang, Houfa Yin, Zhijian Chen, Ke Yao
Autophagy is essential in lens organelle degradation. This study aimed to seek potential autophagy-associated long noncoding RNAs (lncRNAs) and their relative mechanisms in human lens development using the "fried egg" lentoid body (LB) generation system. The expression pattern of LC3B in differentiating LBs was similar to that in developing a mouse lens in vivo. Among the massive lncRNAs expressed with a significant difference between induced pluripotent stem cells (iPSCs) and LBs, lncRNA affecting LC3B (ALB), which was predicted to have a co-relationship with the autophagy marker LC3B, was highly expressed in differentiating lens fibers in LBs...
December 15, 2017: Molecular Therapy. Nucleic Acids
Debojyoti Chakraborty, Maciej Paszkowski-Rogacz, Nicolas Berger, Li Ding, Jovan Mircetic, Jun Fu, Vytautas Iesmantavicius, Chunaram Choudhary, Konstantinos Anastassiadis, A Francis Stewart, Frank Buchholz
Long noncoding RNAs (lncRNAs) have been implicated in diverse biological processes, including embryonic stem cell (ESC) maintenance. However, their functional mechanisms remain largely undefined. Here, we show that the lncRNA Panct1 regulates the transient recruitment of a putative X-chromosome-encoded protein A830080D01Rik, hereafter referred to as transient octamer binding factor 1 (TOBF1), to genomic sites resembling the canonical Oct-Sox motif. TOBF1 physically interacts with Panct1 and exhibits a cell-cycle-specific punctate localization in ESCs...
December 12, 2017: Cell Reports
Rong Weng, Chenqi Lu, Xiaoqin Liu, Guoping Li, Yuanyuan Lan, Jing Qiao, Mingliang Bai, Zhaojie Wang, Xudong Guo, Dan Ye, Zeyidan Jiapaer, Yiwei Yang, Chenliang Xia, Guiying Wang, Jiuhong Kang
Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural differentiation is helpful not only for understanding neural development but also for obtaining high-quality neural progenitor cells required by stem cell therapy of neurodegenerative diseases. Here, we found that long noncoding RNA 1604 (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation, and knockdown of lncRNA-1604 significantly repressed neural differentiation of mouse ESCs both in vitro and in vivo. Bioinformatics prediction and mechanistic analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during neural differentiation...
March 2018: Stem Cells
Michael Alexanian, Daniel Maric, Stephen P Jenkinson, Marco Mina, Clayton E Friedman, Ching-Chia Ting, Rudi Micheletti, Isabelle Plaisance, Mohamed Nemir, Damien Maison, Jasmin Kernen, Iole Pezzuto, Dominic Villeneuve, Frédéric Burdet, Mark Ibberson, Stephen L Leib, Nathan J Palpant, Nouria Hernandez, Samir Ounzain, Thierry Pedrazzini
Enhancers and long noncoding RNAs (lncRNAs) are key determinants of lineage specification during development. Here, we evaluate remodeling of the enhancer landscape and modulation of the lncRNA transcriptome during mesendoderm specification. We sort mesendodermal progenitors from differentiating embryonic stem cells (ESCs) according to Eomes expression, and find that enhancer usage is coordinated with mesendoderm-specific expression of key lineage-determining transcription factors. Many of these enhancers are associated with the expression of lncRNAs...
November 27, 2017: Nature Communications
Meng Amy Li, Paulo P Amaral, Priscilla Cheung, Jan H Bergmann, Masaki Kinoshita, Tüzer Kalkan, Meryem Ralser, Sam Robson, Ferdinand von Meyenn, Maike Paramor, Fengtang Yang, Caifu Chen, Jennifer Nichols, David L Spector, Tony Kouzarides, Lin He, Austin Smith
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression...
August 18, 2017: ELife
Sergio Leone, Dominik Bär, Coenraad Frederik Slabber, Damian Dalcher, Raffaella Santoro
Long non-coding RNAs (lncRNAs) have been implicated in the regulation of chromatin conformation and epigenetic patterns. lncRNA expression levels are widely taken as an indicator for functional properties. However, the role of RNA processing in modulating distinct features of the same lncRNA is less understood. The establishment of heterochromatin at rRNA genes depends on the processing of IGS-rRNA into pRNA, a reaction that is impaired in embryonic stem cells (ESCs) and activated only upon differentiation...
July 2017: EMBO Reports
D Li, Y Ji, F Wang, Y Wang, M Wang, C Zhang, W Zhang, Z Lu, C Sun, M F Ahmed, N He, K Jin, S Cheng, Y Wang, Y He, J Song, Y Zhang, B Li
Regulation of crucial lncRNAs involved in differentiation of chicken embryonic stem cells (ESCs) to spermatogonia stem cells (SSCs) was explored by sequencing the transcriptome of ESCs, primordial germ cells (PGCs) and SSCs with RNA-Seq; analytical bioinformatic methods were used to excavate candidate lncRNAs. We detected expression of candidate lncRNAs in ESCs, PGCs and SSCs and forecasted related target genes. Utilizing wego, david and string, function and protein-protein interactions of target genes were analyzed...
April 2017: Animal Genetics
Kaiqing Lin, Hong Zhan, Junyan Ma, Kaihong Xu, Ruijin Wu, Caiyun Zhou, Jun Lin
Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis...
June 2017: Reproductive Sciences
Katharina Debowski, Charis Drummer, Jana Lentes, Maren Cors, Ralf Dressel, Thomas Lingner, Gabriela Salinas-Riester, Sigrid Fuchs, Erika Sasaki, Rüdiger Behr
Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non-human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus)...
2016: Scientific Reports
Chun-Ying Yu, Hung-Chih Kuo
The trans-spliced noncoding RNA RMST (tsRMST) is an emerging regulatory lncRNA in the human pluripotency circuit. Previously, we found that tsRMST represses lineage-specific transcription factors through the PRC2 complex and NANOG in human pluripotent stem cells (hESCs). Here, we demonstrate that tsRMST also modulates noncanonical Wnt signaling to suppress the epithelial-to-mesenchymal transition (EMT) and in vitro differentiation of embryonic stem cells (ESCs). Our results demonstrate that disruption of tsRMST expression in hESCs results in the upregulation of WNT5A, EMT, and lineage-specific genes/markers...
August 2016: Stem Cells
Srimonta Gayen, Emily Maclary, Michael Hinten, Sundeep Kalantry
X-inactive specific transcript (Xist) long noncoding RNA (lncRNA) is thought to catalyze silencing of X-linked genes in cis during X-chromosome inactivation, which equalizes X-linked gene dosage between male and female mammals. To test the impact of Xist RNA on X-linked gene silencing, we ectopically induced endogenous Xist by ablating the antisense repressor Tsix in mice. We find that ectopic Xist RNA induction and subsequent X-linked gene silencing is sex specific in embryos and in differentiating embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs)...
January 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yan Huang, Yuanyan Xiong, Zhuoheng Lin, Xuyang Feng, Xue Jiang, Zhou Songyang, Junjiu Huang
A recently developed strategy of sequencing alternative polyadenylation (APA) sites (SAPAS) with second-generation sequencing technology can be used to explore complete genome-wide patterns of tandem APA sites and global gene expression profiles. spermatogonial stem cells (SSCs) maintain long-term reproductive abilities in male mammals. The detailed mechanisms by which SSCs self-renew and generate mature spermatozoa are not clear. To understand the specific alternative polyadenylation pattern and global gene expression profile of male germline stem cells (GSCs, mainly referred to SSCs here), we isolated and purified mouse Thy1+ cells from testis by magnetic-activated cell sorting (MACS) and then used the SAPAS method for analysis, using pluripotent embryonic stem cells (ESCs) and differentiated mouse embryonic fibroblast cells (MEFs) as controls...
2015: PloS One
Xin Gui, Haiyan Li, Tianming Li, Hu Pu, Dongdong Lu
Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. Herein, we demonstrate CUDR could enhance the human embryonic stem cells (ESC) differentiation into hepatocyte-like cells by reducing trimethylation on histone H3 twenty-seventh lysine (H3K27me3). On the other hand, excessive CUDR triggers hepatocyte-like cells malignant transformation. Mechanistically, we identify CUDR causes highly upregulated in liver cancer (HULC) and β-catenin abnormal expression by inhibiting HULC promoter methylation and promoting β-catenin promoter-enhancer chromatin looping formation mediated by CUDR-ccctc-binding factor (CTCF) complex, which recruits more RNA polII and P300...
December 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Jan H Bergmann, Jingjing Li, Mélanie A Eckersley-Maslin, Frank Rigo, Susan M Freier, David L Spector
Long noncoding (lnc)RNAs have recently emerged as key regulators of gene expression. Here, we performed high-depth poly(A)(+) RNA sequencing across multiple clonal populations of mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs) to comprehensively identify differentially regulated lncRNAs. We establish a biologically robust profile of lncRNA expression in these two cell types and further confirm that the majority of these lncRNAs are enriched in the nucleus. Applying weighted gene coexpression network analysis, we define a group of lncRNAs that are tightly associated with the pluripotent state of ESCs...
September 2015: Genome Research
Nianwei Lin, Jason Dang, Tariq M Rana
Long non-coding RNAs (lncRNAs) regulate diverse biological functions through mechanisms ascribed to the lncRNA transcript itself. Now in Cell Stem Cell, Yin et al. (2015) use CRISPR/Cas9-mediated genome editing to demonstrate discrete and opposing roles for the lncRNA Haunt transcript and DNA at the HOXA locus during ESC differentiation.
May 7, 2015: Cell Stem Cell
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