Large-scale analysis of the human and mouse transcriptomes

Su, Andrew I.; Cooke, M.; Ching, Keith A.; Hakak, Yaron; Walker, John R.; Wiltshire, Timothy J; Orth, Anthony P.; Vega, Raquel González de; Sapinoso, Lisa M.; Moqrich, Aziz; Patapoutian, Ardem; Hampton, Garret M.; Schultz, Peter G.; Hogenesch, John B.

doi:10.1073/pnas.012025199

Cited by 1,363 publications

(1,319 citation statements)

References 25 publications

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“…25 Four AAC isoforms have been identified in human with distinct expression patterns. 26,27 According to previous reports, [28][29][30] AAC2 and AAC3 are the dominant AACs in ECs. Co-IP confirmed that ISM interacts with AAC2/AAC3 (Figure 5a).…”

Section: Resultsmentioning

confidence: 92%

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Zhang

et al. 2014

Cell Death Differ

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Isthmin (ISM) is a secreted 60-kDa protein that potently induces endothelial cell (EC) apoptosis. It suppresses tumor growth and angiogenesis in mice when stably overexpressed in cancer cells. Although avb5 integrin serves as a low-affinity receptor for ISM, the mechanism by which ISM mediates antiangiogenesis and apoptosis in ECs remain to be fully resolved. In this work, we report the identification of cell-surface glucose-regulated protein 78 kDa (GRP78) as a high-affinity receptor for ISM (K d ¼ 8.6 nM). We demonstrated that ISM-GRP78 interaction triggers apoptosis not only in activated ECs but also in cancer cells expressing high level of cell-surface GRP78. Normal cells and benign tumor cells tend to express low level of cell-surface GRP78 and are resistant to ISM-induced apoptosis. Upon binding to GRP78, ISM is internalized into ECs through clathrin-dependent endocytosis that is essential for its proapoptotic activity. Once inside the cell, ISM co-targets with GRP78 to mitochondria where it interacts with ADP/ATP carriers on the inner membrane and blocks ATP transport from mitochondria to cytosol, thereby causing apoptosis. Hence, ISM is a novel proapoptotic ligand that targets cell-surface GRP78 to trigger apoptosis by inducing mitochondrial dysfunction. The restricted and high-level expression of cell-surface GRP78 on cancer cells and cancer ECs make them uniquely susceptible to ISM-targeted apoptosis. Indeed, systemic delivery of recombinant ISM potently suppressed subcutaneous 4T1 breast carcinoma and B16 melanoma growth in mice by eliciting apoptosis selectively in the cancer cells and cancer ECs. Together, this work reveals a novel ISM-GRP78 apoptosis pathway and demonstrates the potential of ISM as a cancer-specific and dual-targeting anticancer agent.

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Section: Resultsmentioning

confidence: 92%

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Zhang

et al. 2014

Cell Death Differ

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“…A recently published database provides microarray expression data for Affymetrix U95A chip, containing 12,600 probes, and hybridized to 101 different samples [9] from 47 different human tissues and cell lines. These samples are mainly from the normal human physiological state, and therefore this dataset provides a description of the normal mammalian transcriptome.…”

Section: Assignment Of Housekeeping Genesmentioning

confidence: 99%

“…The HK genes, which are transcribed in all somatic cells and under all circumstances, are by nature highly expressed, and therefore should be selected to have shorter introns. We used a recently published database of microarray experiments [9] to identify a set of HK genes. As a further validation step, we checked the Gene Ontology (GO) annotation of these genes.…”

mentioning

confidence: 99%

Human housekeeping genes are compact

2003

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We identify a set of 575 human genes that are expressed in all conditions tested in a publicly available database of microarray results. Based on this common occurrence, the set is expected to be rich in "housekeeping" genes, showing constitutive expression in all tissues. We compare selected aspects of their genomic structure with a set of background genes. We find that the introns, untranslated regions and coding sequences of the housekeeping genes are shorter, indicating a selection for compactness in these genes. 1The amazing diversity of the human body stems from the different expression patterns of genes in different tissues. Although most genes show constitutive expression in only a subset of tissues, some gene products are required for the maintenance of the basal cellular function and are constitutively found in all human cells. These genes are called housekeeping genes (HK genes) [1]. HK genes can be used to calibrate measurements of gene expression [2].They might also help to define the minimal gene complement needed for a human cell [1].Several attempts have been made recently to define the complete set of HK genes [3,4].Microarrays are often used to identify sets of genes that are expressed either ubiquitously or in specific tissues or conditions. However, the technique is technically demanding and prone to artifacts, so independent evidence is often required to confirm the results. In principle, identifying the set of HK genes using microarray data is straightforward; one need only look for genes that are expressed in all tissues and all experimental conditions.Employing such an approach has so far resulted in two lists of HK genes [3,4]. However, problems in probe design, measurement noise and other artifacts introduce inevitable errors in such lists. Because a northern blot experiment for each gene in each tissue is impractical, an independent test is needed to validate any list of HK genes. Here, we report a validation test that uses a recently discovered property of highly expressed genes.The transcription process is both slow and costly; it takes 50 milliseconds [5,6] and two ATP molecules [7] approximately to transcribe a nucleotide. This might be expected to provide selective pressure to make genes as short as functionally possible. The more copies of a gene required for the organism, the stronger this pressure should be. The first demonstration of this principle [8] showed that genes with a large number of expressed sequence tags (ESTs) in public libraries (and hence most mRNAs) have a significantly shorter average intron length than those with fewer ESTs.Here, an implication of this principle is used to validate a set of HK genes. The HK genes, which are transcribed in all somatic cells and under all circumstances, are by nature highly expressed, and therefore should be selected to have shorter introns. We used a recently published database of microarray experiments [9] to identify a set of HK genes. As a further validation step, we checked the Gene Ontology (GO) annotation of thes...

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“…The expression information were retrieved from the GNF SymAtlas (http://symatlas.gnf.org). 21,22 The data were from the human HG-U133A and GNF1H chips, and the mouse GNF1M chip. Our study was focused on 29 orthologous (adult) tissues or cell types (referred to as ,tissues' for simplicity) shared by the mouse and human expression datasets, which are listed as follows: adipose tissue (at), adrenal gland (ag), amygdala (ad), bone marrow (bm), cerebellum (cb), CD4 + Tcells (T4), CD8 + Tcells (T8), dorsal root ganglion (dr), heart (ht), hypothalamus (hp), kidney (kn), liver (li), lung (lu), lymph node (ln), olfactory bulb (oc), ovary (ov), pancreas (pc), pituitary (pi), placenta (pl), prostate (pt), salivary gland (sg), skeletal muscle (sm), testis (ts), thymus (tm), thyroid (tr), tongue (to), trachea (tc), trigeminal (tg), and uterus (ur); the abbreviations in the parentheses were used in the context and figures.…”

Section: Datasetsmentioning

confidence: 99%

Tissue-driven Hypothesis with Gene Ontology (GO) Analysis

Huang

2007

Ann Biomed Eng

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Abstract-Most of the genes are under selective pressure to maintain their expression levels in the tissues. In a recent study, we have proposed a ''tissue-driven'' hypothesis stating that the stabilizing constraints on gene expression levels can be partitioned among tissues; tissues differ in their tolerance to gene expression variances; and the constraints on expression divergence is correlated with the constraints on sequence divergence. Here we further tested the ''tissue-driven'' hypothesis by sub-grouping genes into Gene Ontology (GO) categories. We examined the distribution of tissue expression distance of genes in the major GO categories in the tissues. We also examined the correlation between tissue expression distances and tissue sequence distances or tissue duplicate distances in the major GO categories. Our results have shown that the tissues-specific stabilizing constraints are generally not dominated by particular GO categories. It is also shown that sub-grouping genes into GO categories increased the sensitivity for detecting potential positive factors in expression divergence in the tissues.

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Large-scale analysis of the human and mouse transcriptomes

Cited by 1,363 publications

References 25 publications

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Human housekeeping genes are compact

Tissue-driven Hypothesis with Gene Ontology (GO) Analysis

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