We analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.
Specimen part, Cell line
View SamplesMultiple Myeloma (MM) is an hematological malignancy. MM cells are resistant to X-ray irradiations. We irradiated RPMI 8226 cancer cells with C-ions, which are more energetic than X-ray irradiations. We found that MM cells, RPMI 8226, are also resistant to C-ion irradiations.
HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress.
Cell line
View Samplescomparative expression between stromal MS5 cells treated with (MS5_PD18) or without (MS5_DMSO) MEKi
Interleukin-18 produced by bone marrow-derived stromal cells supports T-cell acute leukaemia progression.
Cell line
View SamplesPhytophthora cinnamomi is a devastating soil-borne oomycete with a very broad host range however there remains a major gap in the understanding of plant resistance responses to the pathogen, furthermore, necrotrophic plant-pathogen interactions, particularly those of root pathogens, remain poorly understood. Zea mays exhibits non-host resistance to the pathogen and has been well characterised as a model species. Using the maize Affymetrix GeneChip array we conducted genome-wide gene expression profiling to elucidate the defence genes and pathways which are induced in the root tissue of a resistant plant species to the pathogen.
Transcriptional profiling of Zea mays roots reveals roles for jasmonic acid and terpenoids in resistance against Phytophthora cinnamomi.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesTranscriptional profiles of the cerebellar endothelial cells from P16 Fz4-/- animals were compared to their wild type littermate controls. The goal is to characterize the long-term effect on the transcriptome of loss of Fz4 signaling in cerebellar endothelial cells.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesEngineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.
Dissecting engineered cell types and enhancing cell fate conversion via CellNet.
Specimen part
View SamplesDecades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of CM maturation which is subsequently required to generate adult myocytes, remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStatCM that indexes CM maturation status. MatStatCM reveals that pluripotent stem cell-derived CMs mature early in culture, but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.
Transcriptional Landscape of Cardiomyocyte Maturation.
Specimen part, Cell line, Time
View SamplesMutations in the poly(A) ribonuclease (PARN) gene cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita (DC)1,2, but how PARN deficiency impacts telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem (iPS) cells from DC patients with PARN mutations, we show that PARN is required for the 3' end maturation of the telomerase RNA component (TERC). Patient cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3' termini reveals that PARN is required for removal of posttranscriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results reveal a novel role for PARN in the biogenesis of TERC, and provide a mechanism linking PARN mutations to telomere diseases. Overall design: mRNA sequencing of fibroblasts, induced pluripotent stem cells, and 293 cell line.
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component.
No sample metadata fields
View SamplesThe telomerase RNA component (TERC) is a critical determinant of cellular self renewal. Poly(A)-specific ribonuclease (PARN) is required for post-transcriptional maturation of TERC. PARN mutations lead to incomplete 3' end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing post-transcriptional 3' oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. Inhibition of the noncanonical poly(A) polymerase PAP-associated domain–containing 5 (PAPD5) increased TERC levels in PARN-mutant patient cells. PAPD5 inhibition was also associated with increases in TERC stability, telomerase activity, and telomere elongation. Our results demonstrate that manipulating post-transcriptional regulatory pathways may be a potential strategy to reverse the molecular hallmarks of telomere disease. Overall design: mRNA sequencing of induced pluripotent stem cells and 293 cell line.
Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease.
Specimen part, Subject
View Samples