Expression profiling of cultured HL-1 cardiomyocytes subjected to hypoxia for 8 hours.
The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.
Cell line
View Sampleswe report the comperative transcriptome analysis of the MMTV-TGF- a female mice thymus tissues Overall design: 3 different fed types
Transcriptome Analysis of the Thymus in Short-Term Calorie-Restricted Mice Using RNA-seq.
Specimen part, Cell line, Subject
View SamplesBreast carcinoma (BC) have been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The shear number of reported signatures has led to speculation that everything is prognostic in BC. Here we show that this ubiquity is an apparition caused by a poor understanding of the inter- relatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers, but who experience a distant metastasis within five years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intra-tumoral heterogeneity.
The prognostic ease and difficulty of invasive breast carcinoma.
Age, Disease stage, Time
View SamplesMicroglia-like cells and neural cells were generated from several hES and hIPS lines. As subset was characterized by RNA seq and compared to expression profiles of published primary and induced samples. ABSTRACT: Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages which have been recognized to play a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and Adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts and resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines, and find that pMGLs derived from MeCP2 mutant hES cells are smaller than their isogenic controls. We further describe a culture platform to study integration and live behavior of pMGLs in organotypic 3D-cultures. This modular differentiation system allows the study of microglia in highly defined conditions, as they mature in response to developmentally relevant cues, and provides a framework to study the long-term interaction of microglia residing in a tissue-like environment. Overall design: Individual donors/genetic backgrounds. Dataset inlcudes 4 differentiated neural progenitor biological replicates (NPC1-4), 2 primary fetal microglia samples as reference, 5 induced microglia samples grown in basal medium (pMGL1-5), 3 induced microglia samples grown in neural conditioned medium (pMGL1-3+NCM)
Efficient derivation of microglia-like cells from human pluripotent stem cells.
Subject
View SamplesWhen assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms'' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Overall design: Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.
Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.
No sample metadata fields
View SamplesOrganoid technology provides the possibility to culture human colon tissue and patient-derived colorectal cancers (CRC) while maintaining all functional and phenotypic characteristics. Labeling of human colon stem cells (CoSCs), especially in normal and benign tumor organoids, is challenging and therefore limits usability of multi-patient organoid libraries for CoSC research. Here, we developed STAR (STem cell Ascl2 Reporter), a minimal enhancer/promoter element that reports transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC fate. Among others via lentiviral infection, STAR minigene labels stem cells in normal as well as in multiple engineered and patient-derived CRC organoids of different stage and genetic make-up. STAR revealed that stem cell driven differentiation hierarchies and the capacity of cell fate plasticity (de-differentiation) are present at all stages of human CRC development. The flexible and user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research on human adult stem cell biology. Overall design: Cells from different colon organoid types were FACS sorted for stem STemness Ascl2 Reporter activity for transcriptome profiling by RNA-seq.
Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene.
Subject
View SamplesPlasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma (MM), namely secondary PCL (sPCL), or as the initial manifestation of disease, namely primary PCL (pPCL). Although presenting signs and symptoms include those seen in MM, pPCL is characterized by several aspects that clearly define more aggressive course. To provide insights into the biology of pPCL, we have investigated the transcriptional profiles of a cohort of 21 newly-diagnosed, homogeneously treated pPCL patients included in a multicenter prospective clinical trial. All but one pPCL had one of the main IGH translocations, whose associated transcriptional signatures resembled those observed in MM. A 503-gene signature was identified that distinguished pPCL from MM, from which emerged 28 genes whose trend in expression levels was found associated with the progressive stages of plasma cell dyscrasia in a large dataset of cases from multiple institutions, including samples from normal donors throughout PCL. The transcriptional pattern of the pPCL series was then evaluated in association with outcome. Three genes were identified having expression levels correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was identified associated with overall survival independently of molecular alterations, hematological parameters and renal function. Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of a subgroup of high-risk pPCL.
Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Specimen part, Disease, Disease stage
View SamplesPrimary plasma cell leukaemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinguished from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Here, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequently altered regions were located at 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%) and 17p (35%). A relevant finding of our study was the identification of a minimal biallelical deletion (1.5 Mb) in 8p21.2 encompassing the putative tumor suppressor gene PPP2R2A that was significantly down-regulated in deleted cases. Mutations of TP53 were identified in 4 cases all but one associated with a monoallelic deletion of the gene, whereas activating mutations of BRAF occurred in one case and were absent for N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferases activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to our understanding of this particular form of plasma cell dyscrasia and to better elucidate the mechanisms of tumor progression in MM.
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Specimen part, Disease, Disease stage
View SamplesAndrogens are required for the development of normal prostate, and they are also linked to the development of prostate cancer.
Proteomic interrogation of androgen action in prostate cancer cells reveals roles of aminoacyl tRNA synthetases.
Specimen part, Cell line
View Samples