Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3’ single-stranded (3’-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses and double-stranded (ds)RNA mapping revealed that 3''-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anti-complementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts. Overall design: Strand-specific transcriptome analysis of biological replicates (1) of WT and xrn1-delta cells of the S288C, W303 and SK1 (n & 2n) genetic background of S. cerevisiae; (2) of WT, dcp2-7 and upf1-delta cells; (3) of WT, xrn1-delta and dcp2-7 cells upon treatment of total RNA with Terminator 5''-Phosphate-Dependent Exonuclease. This record also contains CAGE-Seq analysis in wild-type and decapping-deficient cells of the budding yeast S. cerevisiae.
Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure.
Subject
View SamplesNeural stem cells were sorted according to their activated or quiescent state by flow cytometry using a set of 3 markers (LeX, CD24 and EGFR)
Distinct Molecular Signatures of Quiescent and Activated Adult Neural Stem Cells Reveal Specific Interactions with Their Microenvironment.
Sex, Specimen part
View SamplesHuman Whartons jelly stem cells (hWJSCs) are derived ethically in large amounts from the umbilical cord matrix. Besides their differentiation capabilities, WJSCs also display a notable lack of ability to form teratoma. hWJSCs have been shown to exert immunomodulatory effects and have recently been reported to kill or diminish cancer cell growth. These characteristics are important considerations for their use in cell therapy. In this transcriptome analysis, hWJSCs were profiled using Affymetrix DNA microarrays and compared to a panel of human stem cells and stromal cells. Although hWJSCs are multipotent, they expressed very low levels of the majority of stem cell markers, including POU5F1, NANOG, SOX2 and LIN28. BIRC5 has recently been shown to be required for teratoma formation in SCID mice. The lower levels of BIRC5 expression in hWJSCs compared to hESCs and the very low levels of stem cell markers might account for hWJSCs inability to form teratomas. IL12A which is known to be associated with the induction of apoptosis, was amongst the several cytokines identified to be significantly upregulated in hWJSCs. The ability of hWJSCs to compliment the host immune responses was further highlighted with the GO Biological Process analysis showing high association with immune system, chemotaxis and cell death. The ability to modulate immune responses confers hWJSCs an additional advantage in stem cell therapy and potentially allows hWJSCs as a form of treatment for cancer and immune disorders. In summary, the transcriptome profile of hWJSCs has provided indications on the genetic basis for their biological characteristics in immunomodulatory response, anti-cancer effects, and the lack of teratoma formation.
Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells.
Specimen part
View SamplesPitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Regulatory integration of Hox factor activity with T-box factors in limb development.
Specimen part, Cell line, Subject
View SamplesHuman Whartons jelly stem cells (hWJSCs) are derived ethically in large amounts from the umbilical cord matrix. Besides their differentiation capabilities, WJSCs also display a notable lack of ability to form teratoma. hWJSCs have been shown to exert immunomodulatory effects and have recently been reported to kill or diminish cancer cell growth. These characteristics are important considerations for their use in cell therapy. In this transcriptome analysis, hWJSCs were profiled using Affymetrix DNA microarrays and compared to a panel of human stem cells and stromal cells. Although hWJSCs are multipotent, they expressed very low levels of the majority of stem cell markers, including POU5F1, NANOG, SOX2 and LIN28. BIRC5 has recently been shown to be required for teratoma formation in SCID mice. The lower levels of BIRC5 expression in hWJSCs compared to hESCs and the very low levels of stem cell markers might account for hWJSCs inability to form teratomas. IL12A which is known to be associated with the induction of apoptosis, was amongst the several cytokines identified to be significantly upregulated in hWJSCs. The ability of hWJSCs to compliment the host immune responses was further highlighted with the GO Biological Process analysis showing high association with immune system, chemotaxis and cell death. The ability to modulate immune responses confers hWJSCs an additional advantage in stem cell therapy and potentially allows hWJSCs as a form of treatment for cancer and immune disorders. In summary, the transcriptome profile of hWJSCs has provided indications on the genetic basis for their biological characteristics in immunomodulatory response, anti-cancer effects, and the lack of teratoma formation.
Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells.
Specimen part
View SamplesHuman Whartons jelly stem cells (hWJSCs) are derived ethically in large amounts from the umbilical cord matrix. Besides their differentiation capabilities, WJSCs also display a notable lack of ability to form teratoma. hWJSCs have been shown to exert immunomodulatory effects and have recently been reported to kill or diminish cancer cell growth. These characteristics are important considerations for their use in cell therapy. In this transcriptome analysis, hWJSCs were profiled using Affymetrix DNA microarrays and compared to a panel of human stem cells and stromal cells. Although hWJSCs are multipotent, they expressed very low levels of the majority of stem cell markers, including POU5F1, NANOG, SOX2 and LIN28. BIRC5 has recently been shown to be required for teratoma formation in SCID mice. The lower levels of BIRC5 expression in hWJSCs compared to hESCs and the very low levels of stem cell markers might account for hWJSCs inability to form teratomas. IL12A which is known to be associated with the induction of apoptosis, was amongst the several cytokines identified to be significantly upregulated in hWJSCs. The ability of hWJSCs to compliment the host immune responses was further highlighted with the GO Biological Process analysis showing high association with immune system, chemotaxis and cell death. The ability to modulate immune responses confers hWJSCs an additional advantage in stem cell therapy and potentially allows hWJSCs as a form of treatment for cancer and immune disorders. In summary, the transcriptome profile of hWJSCs has provided indications on the genetic basis for their biological characteristics in immunomodulatory response, anti-cancer effects, and the lack of teratoma formation.
Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells.
Specimen part
View SamplesDeployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance. Overall design: RNA extraction followed by high throughput sequencing (RNA-seq)
Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate.
Specimen part, Cell line, Treatment, Subject
View SamplesThe combinatorial expression of the Hox genes along the body axes, referred to as the HOX code, is a major determinant of cell fate and plays a prevailing role in generating the animal body plan. In developing limb buds, the paralogous group 13 genes of the HoxA and HoxD clusters are essential for patterning the distal-most limb structures, the digits. Inactivation of HOXA13 and HOXD13 transcription factors (HOX13) leads to complete digit agenesis in mice, but how HOX13 regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here we performed genome-wide profiling of HOX13 by chromatin immunoprecipitation and analyzed the transcriptome and chromatin state of wild type early and late-distal limb buds, as well as Hoxa13-/-;Hoxd13-/- compound mutant limb buds. Our results show that inactivation of HOX13 impairs the activation and repression of putative cis-regulatory modules specific to the late-distal limb cells. Loss of HOX13 also disrupts the specific, spatial patterning of gene expression along the proximal-distal axis of the developing limb buds. These results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules. Overall design: Totla mRNAs from dissected distal parts of e11.5 forelimb, of wild-type as well as Hoxa13-/-;Hoxd13-/- mice
Regulatory integration of Hox factor activity with T-box factors in limb development.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View SamplesAnalysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 Neural Precursor cells
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View Samples