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ESCs lncrna

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
Evangelos Pefanis, Jiguang Wang, Gerson Rothschild, Junghyun Lim, David Kazadi, Jianbo Sun, Alexander Federation, Jaime Chao, Oliver Elliott, Zhi-Ping Liu, Aris N Economides, James E Bradner, Raul Rabadan, Uttiya Basu
We have ablated the cellular RNA degradation machinery in differentiated B cells and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core (Exosc3) and nuclear RNase (Exosc10) components of RNA exosome and identified a vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) with emergent functionality. Unexpectedly, eRNA-expressing regions accumulate R-loop structures upon RNA exosome ablation, thus demonstrating the role of RNA exosome in resolving deleterious DNA/RNA hybrids arising from active enhancers...
May 7, 2015: Cell
Yafei Yin, Pixi Yan, Jinlong Lu, Guang Song, Yangyang Zhu, Zhaohui Li, Yi Zhao, Bin Shen, Xingxu Huang, Heng Zhu, Stuart H Orkin, Xiaohua Shen
Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to upregulation or downregulation of HOXA genes, respectively...
May 7, 2015: Cell Stem Cell
Tao Wu, Hugo Borges Pinto, Yasunao F Kamikawa, Mary E Donohoe
Embryonic stem cell (ESC) pluripotency is controlled by defined transcription factors. During cellular differentiation, ESCs undergo a global epigenetic reprogramming. Female ESCs exemplify this process as one of the two X-chromosomes is globally silenced during X chromosome inactivation (XCI) to balance the X-linked gene disparity with XY males. The pluripotent factor OCT4 regulates XCI by triggering X chromosome pairing and counting. OCT4 directly binds Xite and Tsix, which encode two long noncoding RNAs (lncRNAs) that suppress the silencer lncRNA, Xist...
March 10, 2015: Stem Cell Reports
Nataša Savić, Dominik Bär, Sergio Leone, Sandra C Frommel, Fabienne A Weber, Eva Vollenweider, Elena Ferrari, Urs Ziegler, Andres Kaech, Olga Shakhova, Paolo Cinelli, Raffaella Santoro
The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state. How the 3D genome organization is orchestrated and implicated in pluripotency and lineage specification is not understood. Here, we find that maturation of the long noncoding RNA (lncRNA) pRNA is required for establishment of heterochromatin at ribosomal RNA genes, the genetic component of nucleoli, and this process is inactivated in pluripotent ESCs. By using mature pRNA to tether heterochromatin at nucleoli of ESCs, we find that localized heterochromatin condensation of ribosomal RNA genes initiates establishment of highly condensed chromatin structures outside of the nucleolus...
December 4, 2014: Cell Stem Cell
Yongshu Zhang, Jixiang Xia, Qinglin Li, Yuan Yao, Gabriel Eades, Ramkishore Gernapudi, Nadire Duru, Thomas W Kensler, Qun Zhou
Long noncoding RNAs (lncRNAs) have emerged as key regulators of gene expression in embryonic stem cell (ESC) self-renewal and differentiation. In ESCs, lncRNAs are regulated at the genetic level via transcription factor binding to lncRNA gene promoters. Here we demonstrate that the key cytoprotective transcription factor NRF2 controls lncRNA expression in mammary stem cells. By profiling lncRNAs in wild-type and NRF2 knockdown mammary stem cells, we demonstrate that the lncRNA ROR, a regulator of embryonic stem cell pluripotency, is overexpressed upon NRF2 knockdown...
November 7, 2014: Journal of Biological Chemistry
Tomasz Chelmicki, Friederike Dündar, Matthew James Turley, Tasneem Khanam, Tugce Aktas, Fidel Ramírez, Anne-Valerie Gendrel, Patrick Rudolf Wright, Pavankumar Videm, Rolf Backofen, Edith Heard, Thomas Manke, Asifa Akhtar
Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA...
2014: ELife
Yul W Yang, Ryan A Flynn, Yong Chen, Kun Qu, Bingbing Wan, Kevin C Wang, Ming Lei, Howard Y Chang
The WDR5 subunit of the MLL complex enforces active chromatin and can bind RNA; the relationship between these two activities is unclear. Here we identify a RNA binding pocket on WDR5, and discover a WDR5 mutant (F266A) that selectively abrogates RNA binding without affecting MLL complex assembly or catalytic activity. Complementation in ESCs shows that WDR5 F266A mutant is unable to accumulate on chromatin, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and ESC self renewal...
2014: ELife
Federica Santoro, Daniela Mayer, Ruth M Klement, Katarzyna E Warczok, Alexey Stukalov, Denise P Barlow, Florian M Pauler
The imprinted Airn macro long non-coding (lnc) RNA is an established example of a cis-silencing lncRNA. Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter. However, the developmental requirements for Airn initiation of Igf2r silencing and the role of Airn or DNA methylation in maintaining stable Igf2r repression have not been investigated. Here, we use inducible systems to control Airn expression during mouse embryonic stem cell (ESC) differentiation...
March 2013: Development
Carla A Klattenhoff, Johanna C Scheuermann, Lauren E Surface, Robert K Bradley, Paul A Fields, Matthew L Steinhauser, Huiming Ding, Vincent L Butty, Lillian Torrey, Simon Haas, Ryan Abo, Mohammadsharif Tabebordbar, Richard T Lee, Christopher B Burge, Laurie A Boyer
Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor...
January 31, 2013: Cell
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