The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis.
Parvalbumin-Neurons of the Ventrolateral Hypothalamic Parvafox Nucleus Receive a Glycinergic Input: A Gene-Microarray Study.
Specimen part
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Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Specimen part, Cell line, Treatment, Subject
View SamplesWe conducted an in vivo genome-wide CRISPR activation screen to identify genes that accelerate distal metastasis by breast cancer patient-derived circulating tumor cells (CTCs) following direct intravascular inoculation in mice. Regulators of translation and ribosomal proteins were prominent among these, and expression of RPL15, a component of the large ribosome subunit, was sufficient to increase metastatic growth in multiple organs. RPL15 overexpression selectively increases translation of other ribosomal proteins and cell cycle regulators. Unsupervised analysis of single-cell RNA sequencing of freshly-isolated CTCs from breast cancer patients identifies a subset with strong ribosomal and protein translation signatures, correlated with increased proliferative markers, epithelial markers and poor clinical outcome. Thus, ribosome protein expression identifies an aggressive subset of CTCs, whose therapeutic targeting may suppress metastatic progression.
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Specimen part, Cell line, Treatment
View SamplesThe ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice. Overall design: Whole-transcriptome profiling of the cerebral cortex of wild-type control C57BL/6J mice and two independent Plat-/- mice strains on the C57BL/6J background.
Passenger mutations and aberrant gene expression in congenic tissue plasminogen activator-deficient mouse strains.
Age, Specimen part, Cell line, Subject
View SamplesSimilar to embryo-derived stem cells, application of human induced pluripotent stem cells (iPSCs) is limited by our understanding of lineage specification. Here, we demonstrate the ability to generate progenitors and mature cells of the hematopoietic fate directly from human dermal fibroblasts without establishing pluripotency. POU domain activation of hematopoietic transcription factors by ectopic expression of Oct-4, together with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise to granulocytic, monocytic, megakaryocytic, and
Direct conversion of human fibroblasts to multilineage blood progenitors.
Sex, Specimen part, Time
View SamplesGene fusions are known to play critical roles in tumor pathogenesis. However, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. Although real RNA-seq data from cell lines or tumors can be used in testing new fusion detection algorithms, it is impossible to know the true sensitivity or specificity of an algorithm without knowing the "ground truth". For this reason we designed a synthetic control data set to assess the true and false positive and negative fusions of a a new fusion detection algorithm.
Statistical algorithms improve accuracy of gene fusion detection.
Sex, Specimen part
View SamplesHuman induced pluripotent stem cells (hiPSCs) provide an invaluable source for regenerative medicine; but are limited by proficient lineage specific differentiation. Here we reveal that hiPSCs derived from dermal skin fibroblasts (Fib) vs. human cord blood (CB) cells exhibit equivalent and indistinguishable pluripotent properties, but harbor important propensities for neural and hematopoietic lineage differentiation, independent of reprogramming factors used. Genes associated with germ layer specification were identical in both Fib or CB derived iPSCs; whereas patterns of lineage specific marks emerge upon differentiation induction of hiPSCs that were correlated to the cell type of origin used to create hiPSCs. Functionally, CB-iPSCs predominantly differentiate into hematopoietic cells and even adopt definitive hematopoiesis as evidenced by adult -globin positive red blood cell development whereas Fib-iPSCs possess enhanced neural capacity. These clear differentiation propensities come at the expense of other lineages and cannot be overcome with additional external stimuli for alternative cell fates. Moreover, these differences in developmental potential are encoded within cultures of CB vs. Fib derived hiPSCs that can be used to predict differentiation propensity.
Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states.
Specimen part
View SamplesWe discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. Overall design: We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.
No sample metadata fields
View SamplesThe pervasive expression of circular RNA from protein coding loci is a recently discovered feature of many eukaryotic gene expression programs. Computational methods to discover and quantify circular RNA are essential to the study of the mechanisms of circular RNA biogenesis and potential functional roles they may play. In this paper, we present a new statistical algorithm that increases the sensitivity and specificity of circular RNA detection.by discovering and quantifying circular and linear RNA splicing events at both annotated exon boundaries and in un-annotated regions of the genome Unlike previous approaches which rely on heuristics like read count and homology between exons predicted to be circularized to determine confidence in prediction of circular RNA expression, our algorithm is a statistical approach. We have used this algorithm to discover general induction of circular RNAs in many tissues during human fetal development. We find that some regions of the brain show marked enrichment for genes where circular RNA is the dominant isoform. Beyond this global trend, specific circular RNAs are tissue specifically induced during fetal development, including a circular isoform of NCX1 in the developing fetal heart that, by 20 weeks, is more highly expressed than the linear isoform as well as beta-actin. In addition, while the vast majority of circular RNA production occurs at canonical U2 (major spliceosome) splice sites, we find the first examples of developmentally induced circular RNAs processed by the U12 (minor) spliceosome, and an enriched propensity of U12 donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, our algorithm and its results suggest a potentially significant role for circular RNA in human development. Overall design: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kit.
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.
No sample metadata fields
View SamplesNanoemulsion adjuvant affects immune gene expression in dendritic cells.
Distinct pathways of humoral and cellular immunity induced with the mucosal administration of a nanoemulsion adjuvant.
Specimen part
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