This SuperSeries is composed of the SubSeries listed below.
Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.
Sex, Specimen part, Treatment
View SamplesBackground & Aims. Resection of hepatocellular carcinoma (HCC) tumors by partial hepatectomy (PHx) is associated with promoting hepatocarcinogenesis. We have previously reported that PHx promotes hepatocarcinogenesis in the Mdr2-knockout (Mdr2-KO) mouse, a model for inflammation-mediated HCC. Now, we explored the molecular mechanisms underlying the tumor-promoting effect of PHx in these mice. Methods. Using microarrays-based techniques, we compared genomic and transcriptomic profiles of HCC tumors developing in the Mdr2-KO mice either spontaneously or following PHx. Results. PHx accelerated HCC development in these mice by four months. PHx-induced tumors had only amplifications affecting multiple chromosomes and locating mainly near the acrocentric centromeres of murine chromosomes. Four different chromosomal regions were amplified each in at least three tumors. All tumors of untreated mice had chromosomal aberrations, including both deletions and amplifications. Comparison of gene expression profiles revealed a significantly enriched expression of oncogenes, chromosomal instability markers and E2F1 targets in the post-PHx compared to spontaneous tumors. Both tumor groups shared the same frequent amplification at chromosome 18. Here, we demonstrated that one of the regulatory genes encoded by this amplified region, Crem, was over-expressed in the nuclei of murine and human HCC cells in vivo, and that it stimulated proliferation of human HCC cells in vitro. Conclusions: PHx of a chronically inflamed liver directed tumor development to a discrete pathway characterized by amplification of specific chromosomal regions and expression of specific tumor-promoting genes. Crem is a new candidate HCC oncogene frequently amplified in this model and frequently over-expressed in human HCC.
Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.
Specimen part, Treatment
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 SamplesCancer stem cell (CSC) identification relies on transplantation assays of cell sub-populations sorted from fresh tumor samples. Herein, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in-vivo propagating patient derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of EMT, invasion/motility, metastasis and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers. Overall design: Tumorigenic fractions from early-passaged PDX
In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.
Subject
View SamplesThe goal of this study is to elucidate the influence of treadmill training on transcriptome of the upper lumbar spinal cord after thoracic spinal cord hemisection. mRNA profiles of spinal cords at 23 days-post injury with/without treadmill training were generated. The expression levels of 650 genes in the trained animal were increased ( > 2-fold) compared to untrained animals. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion after treadmill training, with biologic replicates, generated by RNA-seq technology. Overall design: The effect of training after spinal cord injury (T9) on the transcriptome of intact upper spinal cord was investigated.
Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View SamplesWe collected globular stage seed compartments from 5 or 7-micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments of an Arabidopsis seed containing a globular stage embryo. For the purposes of this study we broke down the seed into 8 capturable compartments: embyro proper, suspensor, micropylar endosperm, peripheral endosperm, chalazal endosperm, chalazal seed coat, general seed coat, and whole seeds.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
No sample metadata fields
View SamplesWe collected heart stage seed compartments from 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing heart stage embryos. For the purposes of this study we captured 6 compartments: embryo proper, micropylar endosperm, peripheral endosperm, chalazal endosperm, chalazal seed coat and seed coat, as well sets of serial sections encompassing the entire heart stage seed.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View SamplesWe collected linear-cotyledon stage seed compartments from 5 to 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing linear-coyledon-stage embryos. For the purposes of this study we captured 7 compartments: embyro proper, cellularized endosperm, chalazal endosperm, chalazal seed coat, general seed coat, whole seeds and micropylar endosperm.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
No sample metadata fields
View SamplesWe collected mature green seed compartments from 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing mature green-stage embryos. For the purposes of this study we captured 6 compartments: embryo proper, micropylar endosperm, cellularized peripherial endosperm, chalazal endosperm, chalazal seed coat and seed coat, as well sets of serial sections encompassing the entire mature green stage seed.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View Samples