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GSE56082
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARg, which are the master regulators of muscle and adipose differentiation, respectively, confer the robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARg in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells, i.e., lipid-filled myotubes, were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, while exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARg was not down-regulated in myotubes. In PPARg-expressing myotubes, PPARg-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPa, an essential effector of PPARg. Thus, the cross-repressive interactions between MyoD- and PPARg-induced differentiation programs ensure the discrete cell fate decisions.
Publication Title
Antagonism between the master regulators of differentiation ensures the discreteness and robustness of cell fates.
Sample Metadata Fields
Cell line, Treatment
View Samples- Xenopus laevis
- 4 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
A balance between cell survival and apoptosis is essential for animal development. Although proper development involves multiple interactions between germ layers, little is known about the intercellular and intertissue signaling pathways that promote cell survival in neighboring or distant germ layers . We show that serum- and glucocorticoid-inducible kinase 1 (SGK1) promoted ectodermal cell survival during early Xenopus embryogenesis through a non-cell-autonomous mechanism. Dorsal depletion of SGK1 in Xenopus embryos resulted in shortened axes and reduced head structures with defective eyes, and ventral depletion led to defective tail morphologies. Although the gene encoding SGK1 was mainly expressed in the endoderm and dorsal mesoderm, knockdown of SGK1 caused excessive apoptosis in the ectoderm. SGK1-depleted ectodermal explants showed little or no apoptosis, suggesting non-cell-autonomous effects of SGK1 on ectodermal cells. Microarray analysis revealed that SGK1 knockdown increased the expression of genes encoding FADD and caspase-10, components of the death-inducing signaling complex (DISC). Inhibition of DISC function suppressed excessive apoptosis in SGK1-knockdown embryos. SGK1 acted through the transcription factor nuclear factor kappaB to stimulate production of bone morphogenetic protein 7 (BMP7), and overexpression of BMP7 in SGK1-knockdown embryos reduced the abundance of DISC components. We show that phosphoinositide 3-kinase (PI3K) functioned upstream of SGK1, thus revealing an endodermal and mesodermal pathway from PI3K to SGK1 to NF-kappaB that produces BMP7, which provides a survival signal to the ectoderm by decreasing DISC function.
Publication Title
The kinase SGK1 in the endoderm and mesoderm promotes ectodermal survival by down-regulating components of the death-inducing signaling complex.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that the Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation.
Publication Title
ERK5 regulates muscle cell fusion through Klf transcription factors.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
RNA was isolated from siCTRL, siNSUN2 and ALYREF-RIP HeLa cells, and multiple mouse tissues using the TRIzol (Invitrogen) reagent by following the company manual. Approximately 2.5 µg of total RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer’s protocol.The libraries were sequenced using HiSeq3000 (Illumina) or HiSeq2500 in paired-read mode, creating reads with a length of 101 or 125 bp. Sequencing chemistry v2 or v4 (Illumina) was used. Overall design: Examination of gene expressive levels in siCTRL, siNSUN2 and ALYREF-RIP HeLa cells, and multiple mouse tissues
Publication Title
5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m<sup>5</sup>C reader.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Applied de novo assembly, both protein coding and non-coding RNAs were profiled in AFB1 induced HCC and AFB1 resistant liver sample. Compared with normal liver, the perturbation on transcriptome was revealed in multiple aspects, implying the potential mechanism of toxic resistance. Overall design: All rats were randomly divided into control and treated groups according to their weight. Then AFB1 was injected intraperitoneally to treated group in customized schedule. Biopsy was applied every 10 weeks on both groups. Tissues from rats died of HCC were reserved. All rats were sacrificed at 70th week. According to whether tumor formed, liver tissues from animals in treated group were further divided into AFB1 induced tumor sample and AFB1 resistant sample. Both samples were stored for later transcriptome analysis, as well as the normal sample from control group. RNA profiles of all 3 samples were generated by deep sequencing, using Illumina HiSeq2000 platform.
Publication Title
Distinct response of the hepatic transcriptome to Aflatoxin B1 induced hepatocellular carcinogenesis and resistance in rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated genetic approaches identify the molecular mechanisms of Sox4 in early B-cell development: intricate roles for RAG1/2 and CK1ε.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
One of the main objective of this study is to identify Sox4 controlled gene networks and their roles in progenitor B cells.
Publication Title
Integrated genetic approaches identify the molecular mechanisms of Sox4 in early B-cell development: intricate roles for RAG1/2 and CK1ε.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The growth and fruit quality of grapevine are widely affected by abnormal climatic conditions such as water deficit. But how grapevine responds to drought stress is still largely unknown. Here we found that VaNAC26, a member of NAC transcription factor family, was up-regulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardiness wild Vitis species. Ectopic overexpression of VaNAC26 enhanced the drought and salt tolerances in transgenic Arabidopsis. Higher activities of antioxidant enzymes and the lower concentration of H2O2 and O2- were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicate that the reactive oxygen species (ROS) scavenging was enhanced by VaNAC26 in transgenic lines. Microarray based transcriptome analysis reveals that genes related to jasmonic acid (JA) synthesis and signaling were up-regulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on NACRS motif, which was broadly existent in the promoter regions of up-regulated genes in transgenic lines. Endogenous JA content was found increased obviously in VaNAC26-OE-2/3 lines. Our data suggests that VaNAC26 responds to abiotic stresses and may enhance the drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.
Publication Title
Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for reproduction. We performed RNAseq of 3 maturaton staged gonadotrope cell lines, a thyroptrope cell line and NIH-3T3 cells to establish the timing and expression levels of genes involved in gonadotrope maturation. Overall design: Rna-seq of 3 mouse gonadotrope cell lines, 1 mouse thyrotrope cell line and NIH-3T3 cell line
Publication Title
Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types. Overall design: Total of 29 samples were analyzed, which included primary human hepatocytes (PHHs) cultured in different condition in vitro. To figure out how terminally differentiated cells rapidly lose their function in vitro, two PHHs samples were compared, which included 24h-Cultured hepatocytes and fresh primary human hepatocytes (F-PHHs) [GSM2893923 and GSM2893924]. For comparison of global gene expression of primary human hepatocytes (PHHs) maintained with small molecules or sandwich culture for different time periods, sample3-29 were analyzed [GSM2893935 - GSM2893963][GSM3629857-GSM3629862].
Publication Title
Long-term functional maintenance of primary human hepatocytes in vitro.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples