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SRP058979
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
The RAG1 endonuclease, together with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome stability. The sources of RAG1 mistargeting and the mechanisms that have evolved to suppress it are poorly understood. Here, we report the surprising finding that RAG1 binds to thousands of sites in the genome of developing lymphocytes, primarily at active promoters and enhancers. The genome has responded by reducing the abundance of "cryptic" recombination signals near sites of RAG1 binding. This depletion operates specifically on the RSS heptamer, with nonamers enriched at RAG1 binding sites. Reversing this RAG-driven depletion of cleavage sites by insertion of strong recombination signals creates an ectopic hub of RAG-mediated V(D)J recombination and chromosomal translocations. Our findings delineate rules governing RAG binding in the genome, identify areas at risk of RAG-mediated damage, and highlight the evolutionary struggle to accommodate programmed DNA damage in developing lymphocytes. Overall design: RNA-seq profiles of mouse thymocytes
Publication Title
RAG Represents a Widespread Threat to the Lymphocyte Genome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Anamniotes, rodents and man maintain a pool of adult neural stem cells around the central canal in the spinal cord representing an attractive cellular source for endogenous repair. Cell diversity and genes specific for this niche are still ill-defined in mammals. To identify genes specifically expressed in the niche, we microdissected (with laser) the central canal region and the adjacent tissue in human and mice adult tissues. Total RNA was isolated and used to probe affymetrix microarrays
Publication Title
RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1<sup>+</sup> Roof-Plate-Derived Cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The v-erbA oncogene belongs to a superfamily of transcription factors called nuclear receptors, which includes the retinoic acid receptors (RARs) responsible for mediating the effects of retinoic acid (RA). Nuclear receptors bind to specific DNA sequences in the promoter region of target genes and v-erbA is known to exert a dominant negative effect on the activity of the RARs. The repressor activity of v-erbA has been linked to the development of hepatocellular carcinoma (HCC) in a mouse model. We have used microarray analysis to identify genes differentially expressed in hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to RA. We have found that v-erbA can affect expression of RA-responsive genes. We have also identified a number of v-erbA-responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC.
Publication Title
Modulation of expression of RA-regulated genes by the oncoprotein v-erbA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Propose: We used next-generation RNA sequencing (RNA-seq) to characterize the transcriptional changes in primary human melanocytes during recessive Cole disease. Our patient carried missense mutation in the ENPP1 gene (c.358T>C; p.C120R). RNA-seq was performed using mRNA extracted from primary hypo- and hyper-pigmented melanocytes isolated from affected patient and melanocytes from his healthy heterozygous sibling and an aged- and ethnicity-matched control. Results: A pairwise fold-change comparison was performed and genes were computationally filtered using a cutoff of more than 2 fold change and P<0.01. We first compared hyper-pigmented melanocytes to each control individually and then overlapped the results to obtain a list of 1041 up-regulated and 692 down-regulated genes. The same analysis was done for hypo-pigmented melanocytes to found that 535 genes were up-regulated and 520 were down-regulated. Finally, to obtain a profile of the overall differential gene expression, down-regulated genes in hyper and hypo-pigmented cells were overlapped to identify 143 genes that were down-regulated in patient melanocytes compared to controls regardless of pigmentation status. Similar analysis was performed to obtain the list of 172 up-regulated genes. We selected 36 deregulated genes, most of which were associated with melanocyte development and pigmentation signaling pathways, and validated 32 of them by Q-PCR, indicating that our RNA-Seq data was accurate and reliable. Conclusion: Our study represents the first analysis of hypo- and hyper-pigmented primary melanocytes isolated from affected patient versus healthy controls in recessive Cole disese pathology. Overall design: mRNA profiles of hyper- and hypo-pigmented mutant melanocytes, heterozygous and wild type melanocytes were sequenced in triplicate on the Hiseq 2500 High output 100PE
Publication Title
ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcription factors that regulate quiescence, proliferation, and homing of lymphocytes are critical for effective immune system function. In the present study, we demonstrated that the transcription factor ELF4 directly activates the tumor suppressor KLF4 downstream of T cell receptor (TCR) signaling to induce cell cycle arrest in nave CD8+ T cells. Elf4- and Klf4-deficient mice accumulated CD8+CD44hi T cells during steady-state conditions and generated more memory T cells after immunization. The homeostatic expansion of CD8+CD44hi T cells in Elf4-null mice resulted in a redistribution of cells to non-lymphoid tissue due to reduced expression of the transcription factor KLF2, and the surface proteins CCR7 and CD62L. This work describes the combinatorial role of lymphocyte-intrinsic factors in the control of T cell homeostasis, activation and homing.
Publication Title
Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. However, the molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. The alteration in peritumoral microenvironments is believed to play a significant role in inducing epileptogenesis.
Publication Title
Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
To identify the role of the SH3PXD2A-HTRA1 fusion on gene expression in Schwann cells
Publication Title
The genomic landscape of schwannoma.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- NextSeq 500
Description
M端ller cells (MCs) play a crucial role in the retina, and cultured MC lines are an important tool with which to study MC function. Transformed MC lines have been widely used; however, the transformation process can also lead to unwanted changes compared to the primary cells from which they were derived. A monoclonal spontaneously immortalized rat M端ller cell line, SIRMu-1, was derived from primary rat MCs and characterized by RNA-sequencing (in addition to immunofluorescence and western blotting) in comparison to primary MCs and the SV40-immortalized MC line, rMC-1. Overall design: RNA-seq was performed on enriched polyA RNA from primary M端ller cells (4 biological replicates of passage numbers 3-4), SIRMu-1 cells (5 biological replicates of passage numbers 6-20, two of which were cultured in the presence of the antibiotic gentamicin and the antifungal amphotericin B to match the culture conditions of the primary MCs), and rMC-1 cells (3 biological replicates of passage numbers 23-26).
Publication Title
RNA sequencing data of cultured primary rat Müller cells, the spontaneously immortalized rat Müller cell line, SIRMu-1, and the SV40-transformed rat Müller cell line, rMC-1.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGF members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
Publication Title
Smad2 and 3 transcription factors control muscle mass in adulthood.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
B cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A.
Publication Title
Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype.
Sample Metadata Fields
Specimen part
View Samples