乳癌患者における極性タンパクPKCζ発現と化学療法耐性および予後との相関に対する研究

研究科: 千葉大学大学院医学薬学府学位:千大院医薬博甲第医1140号要約博士(医学)千葉大

The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition

Novel targets of the oncogenic miR-17-92 cluster have been identified and the mechanism of regulation of proliferation at the G1/S phase cell cycle transition via the miR-17-5p microRNA has been elucidated

AER Building Blocks for Multi-Layer Multi-Chip Neuromorphic Vision Systems

A 5-layer neuromorphic vision processor whose components communicate spike events asychronously using the address-eventrepresentation (AER) is demonstrated. The system includes a retina chip, two convolution chips, a 2D winner-take-all chip, a delay line chip, a learning classifier chip, and a set of PCBs for computer interfacing and address space remappings. The components use a mixture of analog and digital computation and will learn to classify trajectories of a moving object. A complete experimental setup and measurements results are shown.Unión Europea IST-2001-34124 (CAVIAR)Ministerio de Ciencia y Tecnología TIC-2003-08164-C0

RNA-MATE: a recursive mapping strategy for high-throughput RNA-sequencing data

Summary: Mapping of next-generation sequencing data derived from RNA samples (RNAseq) presents different genome mapping challenges than data derived from DNA. For example, tags that cross exon-junction boundaries will often not map to a reference genome, and the strand specificity of the data needs to be retained. Here we present RNA-MATE, a computational pipeline based on a recursive mapping strategy for placing strand specific RNAseq data onto a reference genome. Maximizing the mappable tags can provide significant savings in the cost of sequencing experiments. This pipeline provides an automatic and integrated way to align color-space sequencing data, collate this information and generate files for examining gene-expression data in a genomic context

A Continuum of Cell States Spans Pluripotency and Lineage Commitment in Human Embryonic Stem Cells

Background: Commitment in embryonic stem cells is often depicted as a binary choice between alternate cell states, pluripotency and specification to a particular germ layer or extraembryonic lineage. However, close examination of human ES cell cultures has revealed significant heterogeneity in the stem cell compartment. Methodology/Principal Findings: We isolated subpopulations of embryonic stem cells using surface markers, then examined their expression of pluripotency genes and lineage specific transcription factors at the single cell level, and tested their ability to regenerate colonies of stem cells. Transcript analysis of single embryonic stem cells showed that there is a gradient and a hierarchy of expression of pluripotency genes in the population. Even cells at the top of the hierarchy generally express only a subset of the stem cell genes studied. Many cells co-express pluripotency and lineage specific genes. Cells along the continuum show a progressively decreasing likelihood of self renewal as their expression of stem cell surface markers and pluripotency genes wanes. Most cells that are positive for stem cell surface markers express Oct-4, but only those towards the top of the hierarchy express the nodal receptor TDGF-1 and the growth factor GDF3. Significance: These findings on gene expression in single embryonic stem cells are in concert with recent studies of early mammalian development, which reveal molecular heterogeneity and a stochasticity of gene expression in blastomeres. Our work indicates that only a small fraction of the population resides at the top of the hierarchy, that lineage priming (co-expression of stem cell and lineage specific genes) characterizes pluripotent stem cell populations, and that extrinsic signaling pathways are upstream of transcription factor networks that control pluripotency

Refining transcriptional programs in kidney development by integration of deep RNA-sequencing and array-based spatial profiling

<p>Abstract</p> <p>Background</p> <p>The developing mouse kidney is currently the best-characterized model of organogenesis at a transcriptional level. Detailed spatial maps have been generated for gene expression profiling combined with systematic <it>in situ </it>screening. These studies, however, fall short of capturing the transcriptional complexity arising from each locus due to the limited scope of microarray-based technology, which is largely based on "gene-centric" models.</p> <p>Results</p> <p>To address this, the polyadenylated RNA and microRNA transcriptomes of the 15.5 dpc mouse kidney were profiled using strand-specific RNA-sequencing (RNA-Seq) to a depth sufficient to complement spatial maps from pre-existing microarray datasets. The transcriptional complexity of RNAs arising from mouse RefSeq loci was catalogued; including 3568 alternatively spliced transcripts and 532 uncharacterized alternate 3' UTRs. Antisense expressions for 60% of RefSeq genes was also detected including uncharacterized non-coding transcripts overlapping kidney progenitor markers, Six2 and Sall1, and were validated by section <it>in situ </it>hybridization. Analysis of genes known to be involved in kidney development, particularly during mesenchymal-to-epithelial transition, showed an enrichment of non-coding antisense transcripts extended along protein-coding RNAs.</p> <p>Conclusion</p> <p>The resulting resource further refines the transcriptomic cartography of kidney organogenesis by integrating deep RNA sequencing data with locus-based information from previously published expression atlases. The added resolution of RNA-Seq has provided the basis for a transition from classical gene-centric models of kidney development towards more accurate and detailed "transcript-centric" representations, which highlights the extent of transcriptional complexity of genes that direct complex development events.</p

Additional file 2: of Sixteen kiwi (Apteryx spp) transcriptomes provide a wealth of genetic markers and insight into sex chromosome evolution in birds

Comma separated file (.csv) of BLAST results and alignment with the North Island brown kiwi genome. Includes the top BLAST hit for each LSK reference contig against NCBI-NR, chicken Ensembl, human Ensembl database, as well as the contig of the kiwi genome assembly to which each transcript mapped and the percent length mapped. (CSV 6520 kb

TGF-β signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis

The molecular mechanisms governing the cell behaviors underlying morphogenesis remain a major focus of research in both developmental biology and cancer biology. TGF-β ligands control cell fate specification via Smad-mediated signaling. However, their ability to guide cellular morphogenesis in a variety of biological contexts is poorly understood. We report on the discovery of a novel TGF-β signaling-mediated cellular morphogenesis occurring during vertebrate gastrulation. Activin/nodal members of the TGF-β superfamily induce the expression of two genes regulating cell adhesion during gastrulation: Fibronectin Leucine-rich Repeat Transmembrane 3 (FLRT3), a type I transmembrane protein containing extracellular leucine-rich repeats, and the small GTPase Rnd1. FLRT3 and Rnd1 interact physically and modulate cell adhesion during embryogenesis by controlling cell surface levels of cadherin through a dynamin-dependent endocytosis pathway. Our model suggests that cell adhesion can be dynamically regulated by sequestering cadherin through internalization, and subsequent redeploying internalized cadherin to the cell surface as needed. As numerous studies have linked aberrant expression of small GTPases, adhesion molecules such as cadherins, and TGF-β signaling to oncogenesis and metastasis, it is tempting to speculate that this FLRT3/Rnd1/cadherin pathway might also control cell behavior and morphogenesis in adult tissue homeostasis