scholarly journals Shared gene expression profiles in developing heart valves and osteoblast progenitor cells

2008 ◽  
Vol 35 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Santanu Chakraborty ◽  
Jonathan Cheek ◽  
Bhuvaneswari Sakthivel ◽  
Bruce J. Aronow ◽  
Katherine E. Yutzey
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Heart Valves ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Precursor Cells ◽  
Negative Regulator ◽  
Endocardial Cushions ◽  
Regulatory Pathways ◽  
Shared Gene

The atrioventricular (AV) valves of the heart develop from undifferentiated mesenchymal endocardial cushions, which later mature into stratified valves with diversified extracellular matrix (ECM). Because the mature valves express genes associated with osteogenesis and exhibit disease-associated calcification, we hypothesized the existence of shared regulatory pathways active in developing AV valves and in bone progenitor cells. To define gene regulatory programs of valvulogenesis relative to osteoblast progenitors, we undertook Affymetrix gene expression profiling analysis of murine embryonic day (E)12.5 AV endocardial cushions compared with E17.5 AV valves (mitral and tricuspid) and with preosteoblast MC3T3-E1 (subclone4) cells. Overall, MC3T3 cells were significantly more similar to E17.5 valves than to E12.5 cushions, supporting the hypothesis that valve maturation involves the expression of many genes also expressed in osteoblasts. Several transcription factors characteristic of mesenchymal and osteoblast precursor cells, including Twist1, are predominant in E12.5 cushion. Valve maturation is characterized by differential regulation of matrix metalloproteinases and their inhibitors as well as complex collagen gene expression. Among the most highly enriched genes during valvulogenesis were members of the small leucine-rich proteoglycan (SLRP) family including Asporin, a known negative regulator of osteoblast differentiation and mineralization. Together, these data support shared gene expression profiles of the developing valves and osteoblast bone precursor cells in normal valve development and homeostasis with potential functions in calcific valve disease.

scholarly journals LncGSEA: a versatile tool to infer lncRNA associated pathways from large-scale cancer transcriptome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanan Ren ◽  
Ting-You Wang ◽  
Leah C. Anderton ◽  
Qi Cao ◽  
Rendong Yang
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Clinical Samples ◽  
Sequencing Data ◽  
Multiple Cancer ◽  
Regulatory Pathways ◽  
Cancer Transcriptome ◽  
Versatile Tool

Abstract Background Long non-coding RNAs (lncRNAs) are a growing focus in cancer research. Deciphering pathways influenced by lncRNAs is important to understand their role in cancer. Although knock-down or overexpression of lncRNAs followed by gene expression profiling in cancer cell lines are established approaches to address this problem, these experimental data are not available for a majority of the annotated lncRNAs. Results As a surrogate, we present lncGSEA, a convenient tool to predict the lncRNA associated pathways through Gene Set Enrichment Analysis of gene expression profiles from large-scale cancer patient samples. We demonstrate that lncGSEA is able to recapitulate lncRNA associated pathways supported by literature and experimental validations in multiple cancer types. Conclusions LncGSEA allows researchers to infer lncRNA regulatory pathways directly from clinical samples in oncology. LncGSEA is written in R, and is freely accessible at https://github.com/ylab-hi/lncGSEA.

scholarly journals Cross-species comparison of genomewide gene expression profiles reveals induction of hypoxia-inducible factor-responsive genes in iron-deprived intestinal epithelial cells

2010 ◽  
Vol 299 (5) ◽  
pp. C930-C938 ◽  
Author(s):  
Zihua Hu ◽  
Sukru Gulec ◽  
James F. Collins
Keyword(s):  
Gene Expression ◽  
Iron Deficiency ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Chip ◽  
Intestinal Epithelial ◽  
Data Set ◽  
Regulatory Pathways ◽  
Metal Ion Homeostasis ◽  
Iron Deficient

Molecular mechanisms mediating the induction of metal ion homeostasis-related genes in the mammalian intestine during iron deficiency remain unknown. To elucidate relevant regulatory pathways, genomewide gene expression profiles were determined in fully differentiated human intestinal epithelial (Caco-2) cells. Cells were deprived of iron (or not) for 6 or 18 h, and Gene Chip analyses were subsequently performed (Affymetrix). More than 2,000 genes were differentially expressed; genes related to monosaccharide metabolism, regulation of gene expression, hypoxia, and cell death were upregulated, while those related to mitotic cell cycle were downregulated. A large proportion of induced genes are hypoxia responsive, and promoter enrichment analyses revealed a statistical overrepresentation of hypoxia response elements (HREs). Immunoblot experiments demonstrated a >60-fold increase in HIF2α protein abundance in iron-deprived cells; HIF1α levels were unchanged. Furthermore, comparison of the Caco-2 cell data set with a Gene Chip data set from iron-deficient rat intestine revealed 29 common upregulated genes; the majority are hypoxia responsive, and their promoters are enriched for HREs. We conclude that the compensatory response of the intestinal epithelium to iron deprivation relates to hypoxia and that stabilization of HIF2α may be the primary event mediating metabolic and morphological changes observed during iron deficiency.

Gene Expression Profiles for Normal Human Bone Marrow-Derived CD34+ Stem Cells and CD34−/CD33+ Myeloid-Committed Progenitor Cells in Response to Daily Granulocyte-Colony-Stimulating Factor (G-CSF) Treatment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4162-4162
Author(s):  
Andrew A.G. Aprikyan ◽  
David Pritchard ◽  
Conrad W. Liles ◽  
Steve Schwartz ◽  
David C. Dale
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Transcription Factors ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Progenitor Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Kinase C ◽  
Chronic Neutropenia

Abstract G-CSF is widely used to accelerate marrow recovery after cancer chemotherapy, to facilitate collection of hematopoietic progenitor cells, and to treat severe chronic neutropenia. Although G-CSF was originally defined as a stimulus for myeloid cell proliferation, it has potent anti-apoptotic properties, affects synthesis of proteins stored in neutrophil granules, and has many other effects on cells of the myeloid lineage. To improve understanding of the molecular and cellular effects of G-CSF, particularly related to its use for the treatment of severe chronic neutropenia, we performed gene expression profile studies using Affymetrix oligonucleotide arrays and purified bone marrow cell sub-populations from normal volunteers treated with daily subcutaneous G-CSF (300 mcg/sc/qd) for five days. Under local anaesthesia, paired marrow aspirates were obtained from the posterior iliac crest before and after 5 daily doses of G-CSF. CD34+ and CD34−/CD33+ cells were purified using Miltenyi immunomagnetic beads. Two rounds of amplification of total RNA isolated from purified CD34+ or CD33+cells was used to obtain sufficient cRNA for hybridization. Expression data from scanned chips were first analyzed using the RMA algorithm. The limma package of the Bioconductor project was used to identify differentially expressed genes. Limma uses an empirical Bayes method to moderate the standard errors of the estimated log-fold changes. The statistical analysis of CD33+ cells revealed that 150 of more than 12,000 genes examined were up- or down-regulated >2-fold in response to G-CSF treatment. The top 10 genes with up- or down-regulated level of expression include clusterin, neutrophil elastase, two transcription factors, gelsolin, Grb2, phospholipase D3, protein kinase C, the major vault protein, and serine-threonine kinase. In the myeloid-committed CD34-/CD33+ progenitor cells, genes with altered expression level represent those with gene products involved in the cell cycle, regulation of apoptosis, the cytoskeleton, the inflammatory response, or serine proteases and transcription factors. Most of the genes up-regulated in CD33+ cells (e.g. neutrophil elastase, phospholipase D, protein kinase C) were down-regulated in CD34-positive cells in response to G-CSF. The results of the comparative analyses revealed the normal signature gene expression profiles for CD34+ and CD34−/CD33+ cells and identified genes that may mediate specific G-CSF effects.

Genome-Wide Profiling of Endothelial Progenitor Cells in Multiple Myeloma: Overlaps with Myeloma Tumor Cells and Common Cancer Gene-Pathways.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 394-394
Author(s):  
Marc J. Braunstein ◽  
Daniel R. Carrasco ◽  
Fabien Campagne ◽  
Piali Mukherjee ◽  
Kumar Sukhdeo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Tumor Cells ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Biomarkers ◽  
Genome Wide

Abstract Background: In multiple myeloma (MM), bone-marrow-derived endothelial progenitor cells (EPCs) contribute to tumor neoangiogenesis, and their levels covary with tumor mass and prognosis. Recent X-chromosome inactivation studies showed that EPCs are clonally restricted in MM. In addition, high-resolution array comparative genomic hybridization (aCGH) found that the genomes of EPCs and MM cells display similar chromosomal gains and losses in the same patient. In this study, we performed an integrative analysis of EPCs and tumor cells by genome-wide expression profiling, and applied a bioinformatics approach that leverages gene expression data from cancer datasets to mine MM gene pathways common to multiple tumor tissues and likely involved in MM pathogenesis. Methods: Confluent EPCs (>98% vWF/CD133/KDR+ and CD38−) were outgrown from 22 untreated MM patients’ bone marrow aspirates by adherence to laminin. The fractions enriched for tumor cells were >50% CD38+. For gene expression profiling, total RNA from EPCs, MM cells, and control HUVECs were hybridized to cDNA microarrays, and comparisons were made by analysis of variance. Results: Two sets of EPC gene profiles were of particular interest. The first contained genes that differ significantly between EPCs and HUVEC, but not between EPCs and tumor (Profile 1). We hypothesize that this profile is a consequence of the clonal identity previously reported between EPCs and tumor, and that a subset of these genes is largely responsible for MM progression. The second set of important EPC genes are differentially regulated compared both to HUVECs and to tumor cells (Profile 2). These genes may represent the profile of EPCs that are clonally diverse from tumor cells but nevertheless display common gene expression patterns with other cancers. Profile 2 genes may also represent genes that confer a predisposition to clonal transformation of EPCs. When genes in Profile 1 and Profile 2 were overlapped with published lists of cancer biomarkers, significant similarities (P<.05) were apparent. The largest overlaps were observed with the HM200 gene list, a list composed of 200 genes most consistently differentially expressed in human/mouse cancers (Campagne and Skrabanek, BMC Bioinformatics 2006). More than 80% of genes in either EPC profile have not been previously characterized in MM, but have been identified as cancer biomarkers in other cancer studies. These genes will be presented and discussed in the context of MM. Current studies are aimed at integrating Profile 1 and Profile 2 genes in each patient with chromosomal copy number abnormalities (CNAs) found in EPCs, and also with clinical stage and disease severity, in order to elucidate the pathogenic information that the profiles hold. Conclusions: The genomes of EPCs display ranges of overlap with tumor cells in MM, evidenced by gene expression profiles with varying similarity to those found in MM tumor cells. More importantly, MM EPC gene expression profiles, in contrast to normal endothelial cells, contain cancer biomarker genes in tumors not yet associated with MM. Results strongly support the concept that EPCs are an integral part of the neoplastic process in MM.

Gene Expression Profiles and Retinal Potential of Stem/Progenitor Cells Derived from Human Iris and Ciliary Pigment Epithelium

2012 ◽  
Vol 8 (4) ◽  
pp. 1163-1177 ◽  
Author(s):  
Srilatha Jasty ◽  
Priyadharashni Srinivasan ◽  
Gunisha Pasricha ◽  
Nivedita Chatterjee ◽  
Krishnakumar Subramanian
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Gene Expression Profiles ◽  
Human Iris
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