Metazoan development depends on accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation is brought about by global changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell fate determination is less well understood. Using a human embryonic stem cell model, we identified the vertebrate-specific ubiquitin ligase Cul3KBTBD8 as an essential regulator of neural crest cell formation. Cul3KBTBD8 monoubiquitylates NOLC1 and its paralog TCOF1, whose mutation underlies the developmental disease Treacher Collins Syndrome that is characterized by a loss of cranial neural crest cells. Ubiquitylation of NOLC1 and TCOF1 drives formation of a platform that connects RNA polymerase I with ribosome modification enzymes, thereby altering the translational program of differentiating cells to support the generation of neural crest cells. We conclude that the dynamic regulation of ribosome function is an important feature of cell fate determination.
Cell-fate determination by ubiquitin-dependent regulation of translation.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands.
Specimen part, Cell line
View SamplesIn order to study the effects of Kdm2b binding at CpG islands, Kdm2b was knocked down in mouse embryonic stem cells using shRNA and gene expression profiled using Affymetrix arrays
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands.
Specimen part
View Samples16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines
Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions.
Cell line
View SamplesAlveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Comparative transcriptome analysis of equine alveolar macrophages.
Treatment
View SamplesMHCaCre induced knockout of Fog2flox.
Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart.
Sex, Specimen part, Treatment
View SamplesBreast cancer develops through the accumulation of genomic changes in the ductal epithelia cells of normal breast tissue. A determination of whether gene expression changes in ductal cells is associated with an increased risk for breast cancer is needed. We sought to determine if the global gene expression profiles of ductal cells of women at high risk for breast cancer or with cytologic ductal epithelial atypia differed from those of women at normal risk or without cytologic atypia.
Characteristics of Breast Ducts in Normal-Risk and High-risk Women and Their Relationship to Ductal Cytologic Atypia.
Specimen part, Disease stage
View SamplesTL1A contributes to the pathogenesis of several chronic inflammatory diseases, including Inflammatory Bowel Diseases by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong co-stimulation of these TH subsets particularly of mucosal CCR9+ T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. Here, we investigated the function of TL1A on human TH17 cells. TL1A together with TGF- IL-6, and IL-23 enhanced the secretion of IL-17 and IFN- from human CD4+ memory T cells. TL1A induced the expression of the transcription factors BATF and T-bet that correlated with the secretion of IL-17 and IFN-. In contrast, TL1A alone induced high levels of IL-22 in memory CD4+ T cells and committed TH17 cells. However, TL1A did not enhance expression of IL-17A in TH17 cells. Expression of the transcription factor aryl hydrocarbon receptor that regulates expression of IL-22 was not affected by TL1A. We performed transcriptome analysis of TH17 cells to determine genes that are transcriptionally regulated by TL1A. transcriptome analysis revealed increased expression of IL-9 in response to TL1A.
The TNF family member TL1A induces IL-22 secretion in committed human T<sub>h</sub>17 cells via IL-9 induction.
Specimen part
View SamplesApproximately 60-70% of patients with pulmonary sarcoidosis have a good outcome, with disease that resolves spontaneously. It is unclear why some patients progress to fibrotic disease, and there is currently no marker that differentiates these patients from those with self-limiting lung disease.
Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis.
Sex, Age, Specimen part
View SamplesAnalysis of gene expression in Mouse E14-TG2a.IV strain ES cells Overall design: Single end RNA-seq analysis of PolyA selected RNA from E14-TG2a.IV ES cells
Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.
Specimen part, Subject
View Samples