Samples 1-4 report RNA-seq transcriptome profiling of the L-Proline- (L-Pro) and bFgf/ActivinA- (F/A) derived mCherry+/eGFP+ (yellow) ESC population, using the Illumina HiSeq platform. Whole-genome expression revealed that more than 1000 genes were significantly deregulated in L-Pro- and F/A-induced cells compared to control (mCherry+/eGFP- red cells) and the two population shared up to 75% of deregulated genes with the same deregulation trend. Specifically, the pluripotency-associated genes were downregulated either at similar level (Nanog, Klf2, Klf4 and Gbx2) or at lower levels (up to 10 times) (Dppa 2, 3, 4, 5a, Rex1, Esrrb) in F/A- compared to L-Pro-treated cells. Interestingly, mesendodermal-related genes (e.g. Brachyury, Cer1, Dkk1, Eomes, Foxa2, and Sox17) were induced in both conditions but at significant higher levels in F/A- compared to L-Pro-treated cells. The transcriptome analysis of mCherry+/eGFP+ (yellow) cells supported the idea that L-Pro mimics F/A in inducing a naïve to primed transition, and suggested that it exerted a milder (weaker) effect. Samples 5-14 report RNA-seq transcriptome profiling of the mir-290_mCherry/mir-302_eGFP dual reporter ESCs (DRESCs) bulk culture, grown in FBS/LIF ± VitaminC (VitC) and L-Proline (L-Pro) and compared them to the standard naive/2i and primed/bFgf/ActivinA-EpiSCs (F/A), using the Illumina HiSeq platform. Whole-genome expression identified around 7900 deregulated genes in the different conditions, (fold change=2 and pvalue<0.05). Principal component analysis (PCA) placed VitC between 2i and untreated control, and L-Pro between control and F/A. Accordingly, a set of pluripotency-associated genes was expressed at higher level in 2i and VitC conditions, while downregulated in L-Pro and F/A, compared to control. Conversely, priming markers were downregulated in 2i and VitC and upregulated in L-Pro and F/A compared to control The transcriptome analysis supported that VitC- and L-Pro captured alternative pluripotency states that can be likely placed between naïve/2i and primed/F/A states. Overall design: RNA-seq profiling of ESCs grown in FBS/LIF ± VitC, 2i, L-Pro or F/A, using the Illumina HiSeq platform
Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
Cell line, Subject
View SamplesFollowing androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics.
Longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways to androgen independence.
No sample metadata fields
View SamplesSTAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by 2 separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knock-down of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-beta cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.
In vivo identification of novel STAT5 target genes.
No sample metadata fields
View SamplesWe have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves.
Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.
Age, Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View Samples