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SRP054257
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Insults to cellular health cause p53 protein accumulation and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel inhibitory role of PATZ1 on the p53 protein marks it as a proto-oncogene. PATZ1 deficient cells have reduced proliferative capacity which we assess by RNASeq and real time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage inducing drug doxorubicin results in the loss of the PATZ1 transcription factor, as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53 dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. Overall design: RNA-seq was used to define differentially expressed genes in wild-type and PATZ1-/- MEFs. Each sample was represented in triplicate.
Publication Title
PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Celiac disease (CeD) is an intestinal immune-mediated disorder caused by gluten ingestion in genetically predisposed subjects. CeD is characterized by villous atrophy, altered intestinal permeability, crypt hyperplasia and innate and adaptive immune response. This study aimed to develop and validate the use of intestinal organoids from celiac patients to study CeD. A repository of organoids from duodenum of non-celiac and celiac patients was generated and characterized accordingly to standard procedures. RNA-seq analysis was employed to study the global gene expression program of CeD (n=3) and non-CeD (n=3) organoids sets. While the three celiac derived organoids shared similar transcriptional signatures the NC samples set appeared more heterogeneous. We found 486 genes differentially expressed between the two groups. Of them, 299 genes were downregulated (FC<2; FDR<0.05) and 187 were upregulated in CeD (FC >2; FDR<0.05). We observed CeD organoids had significantly altered expression of genes associated with barrier function, innate immunity, and stem cell function. Overall design: mRNA profiles of 3 non-celiac healthy controls and 3 celiac organoids derived from duodenal biopsies.
Publication Title
Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500
Description
Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is extremely inefficient, complicating mechanistic studies. Here, we identified and molecularly characterized rare, early intermediates poised to reprogram with up to 100% efficiency, without perturbing additional genes or pathways. Analysis of these cells uncovered transcription factors (e.g., Tfap2c, Bex2), which are critical for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed a previously unappreciated early wave of DNA demethylation, which is uncoupled from de novo methylation of somatic regions late in reprogramming. Overall, our study underscores the importance of investigating the rare intermediates poised to produce iPSCs, provides novel insights into the mechanisms of reprogramming, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change. Overall design: RNA-seq of reprogramming intermediates (11 cell types in triplicate).
Publication Title
Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is extremely inefficient, complicating mechanistic studies. Here, we identified and molecularly characterized rare, early intermediates poised to reprogram with up to 100% efficiency, without perturbing additional genes or pathways. Analysis of these cells uncovered transcription factors (e.g., Tfap2c, Bex2), which are critical for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed a previously unappreciated early wave of DNA demethylation, which is uncoupled from de novo methylation of somatic regions late in reprogramming. Overall, our study underscores the importance of investigating the rare intermediates poised to produce iPSCs, provides novel insights into the mechanisms of reprogramming, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change. Overall design: RNA-seq of reprogramming intermediates (6 cell types in duplicate).
Publication Title
Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 84 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
The preoptic area (POA) of the hypothalamus is known to be crucial for sleep generation, but the spatial intermingling of sleep- and wake-promoting neurons makes it difficult to dissect the sleep control circuit. Here we identified a population of POA sleep-promoting neurons based on their projection target. Using a lentivirus for retrograde labeling with channelrhodopsin-2 (ChR2) followed by optogenetic manipulation and recording, we found that the POA GABAergic neurons projecting to the tuberomammillary nucleus (TMN) are both sleep active and sleep promoting. Cell type- and projection-specific rabies tracing revealed the presynaptic inputs to these neurons, including an amygdala GABAergic input that promotes wakefulness. Using single-cell RNA-seq, we identified several molecular markers for these neurons, and optogenetic activation of the POA neurons labeled by these markers confirmed their sleep-promoting effects. Together, these findings define a group of sleep-promoting neurons functionally, anatomically, and genetically. Overall design: Single-cell RNA-Seq of retrogradely-labeled POA neurons projecting to the tuberomammillary nucleus (TMN).
Publication Title
Identification of preoptic sleep neurons using retrograde labelling and gene profiling.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, -catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths
Publication Title
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cellular senescence is a tumor suppressor mechanism, and immortalization facilitates neoplastic transformation. Both mechanisms may be highly relevant to hepatocellular carcinoma (HCC) development and its molecular heterogeneity. Cellular senescence appears to play a major role in liver diseases. Chronic liver diseases are associated with progressive telomere shortening leading senescence that is observed highly in cirrhosis, but also in some HCC. We previously described the generation of immortal and senescence-programmed clones from HCC-derived Huh7 cell line.
Publication Title
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silico dissection of mixed phenotypes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the differentiation process of embryonic stem cells into hemangioblasts, gene expression profiles of ES, EB and Blast cells (BL) were analyzed.
Publication Title
GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silico dissection of mixed phenotypes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the differentiation process of embryonic stem cells into hemangioblasts, gene expression profiles of ES, EB and Blast cells (BL) were analyzed.
Publication Title
GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silico dissection of mixed phenotypes.
Sample Metadata Fields
No sample metadata fields
View Samples