Biomedical subjects

Xuping Fu

Publications and source records attributed to Xuping Fu.

9 recordsLinked to original sources

PubMed2007

Hepatic differentiation and transcriptional profile of the mouse liver epithelial progenitor cells (LEPCs) under the induction of sodium butyrate.

The liver regenerates by progenitor cells when it is damaged in chronic liver diseases and extensive damage. The progenitor cells, also termed "oval cells" according to their morphological traits, can differentiate into hepatocytes and bile duct cells in vivo. To better understand the transcriptional pattern that accompanies the hepatic differentiation of oval cells, we applied cDNA microarray to analyze the oval cell-derived liver epithelial progenitor cells (LEPCs) during in vitro induced differentiation. Upon exposure to sodium butyrate, a histone deacetylase inhibitor, cultured LEPCs differentiate and express functional hepatocyte markers albumin, tryptophan 2, 3-dioxygenase and alcohol dehydrogenase. For expression profiling, cells were harvested at 6 h, 12 h, 1 d, 3 d and 7 d after exposure to sodium butyrate. After analyzing the microarray data by SOM clustering, total of 796 differentially regulated genes were grouped into 48 clusters. Consistent with the phenotype change of LEPCs after sodium butyrate treatment, many hepatocyte functional genes are revealed by analyzing the clusters containing genes up-regulated through all the time points. The clusters, containing down-regulated genes immediately after the induction, are also analyzed. The microarray data was validated by analyzing the expression of selected genes by quantitative real-time PCR. A set of genes expressed synergistically in these clusters may play a central role during the process of differentiation. Sodium butyrate decreases cyclin B1 and Cdk4 expression, which would be associated with LEPCs growth arrest shortly after treatment. Bmi1, a polycomb group protein, is also down-regulated immediately after treatment and remains at a low level during the induction. These findings highlight the key molecular mechanisms by which sodium butyrate, mediates its effects on cell growth arrest and induction of differentiation. In conclusion, our data reflect a global view of gene expression during hepatic differentiation of LEPCs induced by sodium butyrate.

Animals↗

PubMed2007

Identification of genes differentially regulated by transcription factor, AP-2delta.

In an effort to better understand the transcriptional program regulated by transcription factor, AP-2delta, we used cDNA microarray to evaluate the relative expression of human genes in AD293 cells by exogenous expression of AP-2delta. Microarray showed 29 genes that were up-regulated and 39 genes with a down-regulated expression pattern. Among the identified genes were those encoding transcription factors, signal transduction molecules, kinases, as well as genes regulating cell growth, differentiation, and cell adhesion, a set of genes suggested to be regulated by AP-2. The results of microarray was validated for some regulated genes by real-time PCR analysis. These observations shed novel insight into the mechanism of AP-2delta action and provide a range of target genes for further investigation.

Binding Sites↗

PubMed2006

LS-CAP: an algorithm for identifying cytogenetic aberrations in hepatocellular carcinoma using microarray data.

Biological techniques such as Array-Comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and affymetrix single nucleotide pleomorphism (SNP) array have been used to detect cytogenetic aberrations. However, on genomic scale, these techniques are labor intensive and time consuming. Comparative genomic microarray analysis (CGMA) has been used to identify cytogenetic changes in hepatocellular carcinoma (HCC) using gene expression microarray data. However, CGMA algorithm can not give precise localization of aberrations, fails to identify small cytogenetic changes, and exhibits false negatives and positives. Locally un-weighted smoothing cytogenetic aberrations prediction (LS-CAP) based on local smoothing and binomial distribution can be expected to address these problems. LS-CAP algorithm was built and used on HCC microarray profiles. Eighteen cytogenetic abnormalities were identified, among them 5 were reported previously, and 12 were proven by CGH studies. LS-CAP effectively reduced the false negatives and positives, and precisely located small fragments with cytogenetic aberrations.

Algorithms↗

PubMed2006

Genes differentially expressed in responsive and refractory acute leukemia.

DNA microarray in 22 patients with acute leukemia revealed genes which were differentially expressed. Ribosomal protein SA (RPSA), minichromosome maintenance deficient 2 (MCM2) and heterogeneous nuclear ribonucleoprotein A1 (HNRPA1) were significantly upregulated (p<0.05, t test) in refractory patients, suggesting that they may play a role in refractoriness in acute leukemia and could be biomarkers of prognosis.

Adolescent↗

PubMed2005

Finding dominant sets in microarray data.

Clustering allows us to extract groups of genes that are tightly coexpressed from Microarray data. In this paper, a new method DSF_Clust is developed to find dominant sets (clusters). We have preformed DSF_Clust on several gene expression datasets and given the evaluation with some criteria. The results showed that this approach could cluster dominant sets of good quality compared to kmeans method. DSF_Clust deals with three issues that have bedeviled clustering, some dominant sets being statistically determined in a significance level, predefining cluster structure being not required, and the quality of a dominant set being ensured. We have also applied this approach to analyze published data of yeast cell cycle gene expression and found some biologically meaningful gene groups to be dug out. Furthermore, DSF_Clust is a potentially good tool to search for putative regulatory signals.

Algorithms↗

PubMed2005

Analysis of the factors affecting the accuracy of detection for single base alterations by oligonucleotide microarray.

The oligonucleotide microarray, a high-throughput polymorphism detection technology, holds great promise for the characterization of complex genetic variance. To achieve greater sensitivity and specificity for it to be an effective platform technology we present results and discuss some of the factors influencing signal intensities and single-mismatch discrimination in array-based mutation/SNP detection. Probes with a series of concentrations were spotted onto the slide in order to find the optimal concentration with the identifiable satisfying signals and the stable ratios between matched and mismatched probes. It was found that under our experimental conditions, when the initial probe concentration is higher than the maximum immobilization capability of the slide (7.5 microM), the hybridization signal will be saturated and the ratio between matched and mismatched probes will be more stable than at a lower probe concentration. Considering the cost of probes and the systematic stability, a constant spotting concentration of 10 microM was selected. The stability of different types of mismatched oligo-DNA duplexes on the glass surface was also confirmed. The results show that the order of stability of mismatched oligo-DNA duplexes on a glass surface is in general agreement with previous reports conducted using liquid and polyacrylamide gel pads. This suggests that the influence of the mismatched base pair on the stability of the duplex in a solid hybridization system is similar to that in the solution hybridization environment.

Nucleic Acid Heteroduplexes↗

PubMed2004

Cloning and expression of human GTDC1 gene (glycosyltransferase-like domain containing 1) from human fetal library.

The glycosyltransferases (GTs) catalyze the synthesis of the carbohydrate portions of glycoproteins, glycolipids, and proteoglycans. Here we report the cloning and characterization of a novel human GTDC1 (glycosyltransferase-like domain containing 1) gene, which locates on human chromosome 2q22. The GTDC1 cDNA is 2954 bp in length, encoding a putative protein of 458 amino acids. At protein level human GTDC1 has 75 and 37% identity with its homologous counterparts in the mouse and fruitfly, respectively. RT-PCR analysis revealed its relatively high expression level in the adult lung, spleen, testis, and peripheral blood leukocyte.

Amino Acid Sequence↗

PubMed2003

Determining a detectable threshold of signal intensity in cDNA microarray based on accumulated distribution.

In microarray data mining, one of the key problems is how to handle weak signals. Based on a bent piecewise linear accumulated distribution generally found in the microarray data, a new detectable threshold finding method is proposed to filter genes with unreliable information in this paper. More reliable and reproducible data is produced for the subsequent data mining.

DNA, Complementary↗

PubMed2003

Cloning and characterization of human synaptotagmin 10 gene.

Synaptotagmin (Syt) is a membrane protein family of secretory vesicles, abundant in neural and some endocrine cells. All the members of this family contain one transmembrane region and two conserved C2 domains. Here we reported a new human Syt 10 gene isolated when screening a human fetal brain cDNA library. This cDNA clone is 3287 bp and contains an open reading frame from 299 to 1870 encoding a putative protein of 523 amino acids. It shares 94.6 and 94.8% homology to rat Syt 10 and mouse Syt 10 at protein level, respectively. RT-PCR result showed that it is expressed only in pancreas, lung and kidney.

Amino Acid Sequence↗