Gene Expression 14(6) Abstracts

Return to Gene Expression main page>

Gene Expression, Vol. 14, pp. 307–319, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12717040569866
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Differential Expression of Shh and BMP Signaling in the Potential Conversion of Human Adipose Tissue Stem Cells Into Neuron-Like Cells In Vitro

Alejandra Cardozo,* Marcelo Ielpi,* Daniel Gómez,† and Pablo Argibay*

*Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
†Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, Buenos Aires, Argentina

The nervous system (NS) has a limited self-repair capability and adult neurogenesis is limited to certain regions of the brain. This generates a great interest in using stem cells to repair the NS. Previous reports have shown the differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) in neuron-like cells when cultures are enriched with growth factors participating in embryonic and adult neurogenesis. Therefore, it could be thought that there exists a functional parallelism between neurogenesis and neuronal differentiation of ASCs. For this reason, the goal of this work was to study the differential gene expression of Shh and BMP genetic pathways involved in cell fate determination and proliferation. In this study we demonstrated that hASCs are endowed with active Hedgehog and BMP signaling pathways through the expression of genes of both cascades and that their expressions are downregulated after neuronal induction. This idea is in accordance with the facts that Shh and BMP signaling is involved in the maintenance of cells with stem cells properties and that proliferation decreases during the process of differentiation. Furthermore, Noggin expression was detected in induced hASCs whereas there was no expression in noninduced cells, which indicates that these cells are probably adopting a neuronal fate because noggin diverts neural stem cells from glial to neuronal fate. We also detected FM1-43 and synaptophisin staining, which is evidence of the presence of putative functional presynaptic terminals, a neuron-specific property. These results could partially contribute to the elucidation of the molecular mechanisms involved in neuronal differentiation of adult human nonneural tissues.

Key words: hASCs; Neuronal differentiation; Shh signaling; BMP signaling

Address correspondence to Pablo Francisco Argibay, Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Potosí 4240—8° piso—C1199ACL, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. Tel: +54 11 4959 0200 # 8919; Fax: +54 11 4959 0200 # 5355; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 14, pp. 321–336, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12717040569820
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Quantitative Gene Expression Profiles in Real Time From Expressed Sequence Tag Databases

Vincent A. Funari,*1 Konstantin Voevodski,*2 Dimitry Leyfer,†3 Laura Yerkes,* Donald Cramer,* and Dean R. Tolan*†

*Biology Department, Boston University, Boston, MA, USA
†Bioinformatics Program, Boston University, Boston, MA, USA

An accumulation of expressed sequence tag (EST) data in the public domain and the availability of bioinformatic programs have made EST gene expression profiling a common practice. However, the utility and validity of using EST databases (e.g., dbEST) has been criticized, particularly for quantitative assessment of gene expression. Problems with EST sequencing errors, library construction, EST annotation, and multiple paralogs make generation of specific and sensitive qualitative and quantitative expression profiles a concern. In addition, most EST-derived expression data exists in previously assembled databases. The Virtual Northern Blot (VNB) (http://tlab.bu.edu/vnb.html) allows generation, evaluation, and optimization of expression profiles in real time, which is especially important for alternatively spliced, novel, or poorly characterized genes. Representative gene families with variable nucleotide sequence identity, tissue specificity, and levels of expression (bcl-xl, aldoA, and cyp2d9) are used to assess the quality of VNB’s output. The profiles generated by VNB are more sensitive and specific than those constructed with ESTs listed in preindexed databases at UCSC and NCBI. Moreover, quantitative expression profiles produced by VNB are comparable to quantization obtained from Northern blots and qPCR. The VNB pipeline generates real-time gene expression profiles for single-gene queries that are both qualitatively and quantitatively reliable.

Key words: Expressed sequence tag (EST); Transcriptomics; Bioinformatics; Quantitative PCR; Northern blot

1Present address: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 and Department of Pediatrics, DavidGeffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
2Present address: Department of Computer Science, Boston University, Boston, MA 02215, USA.
3Present address: MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, MA 02129, USA.
Address correspondence to Dean R. Tolan, Biology Department, Boston University, 5 Cummington Street, Boston, MA 02215, USA. Tel: 617-353-5310; Fax: 617-358-0338; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 14, pp. 337–344, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12717040569901
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Developmental and Tissue-Specific Regulation of Hepatocyte Nuclear Factor 4-α (HNF4-α) Isoforms in Rodents

Samena Dean, Justin I. Tang, Jonathan R. Seckl, and Moffat J. Nyirenda

Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

Hepatocyte nuclear factor 4-α (HNF4-α) regulates expression of a number of genes in several metabolic organs. The HNF4-á gene has two promoters and encodes at least nine isoforms through differential splicing. In mouse liver, transcription initiates at promoter 2 (P2) during fetal life, but switches to P1 at birth. Developmental and tissue-specific expression of HNF4-α in other organs is largely unknown. Here, we examined expression of P1- and P2-derived transcripts in a number of mouse and rat tissues. Both P1 and P2 were active in mouse fetal liver, but P2-derived isoforms were detected 50% more abundantly than P1 transcripts. Conversely, the adult mouse liver expressed significantly higher levels of P1- than P2-derived mRNA. In contrast, in the rat, P1 was used more predominantly in both fetal and adult liver. Exposure of fetal rats to the synthetic glucocorticoid dexamethasone caused suppression of P2 while enhancing hepatic expression of transcripts from P1. This was associated with increased expression of erythropoietin and phosphoenolpyruvate carboxykinase, which are key HNF4-α targets in the liver. Unlike liver, the kidney and stomach used promoters more selectively, so that only P1-derived isoforms were detected in fetal and adult kidneys in mice or rats, whereas the stomach in both species expressed P2-derived transcripts exclusively. No significant HNF4-α mRNA was detected in the spleen. These data reveal striking developmental and tissue-specific variation in expression of HNF4-α, and indicate that this can be influenced by environmental factors (such as exposure to glucocorticoid excess), with potential pathophysiological consequences.

Key words: Hepatocyte nuclear factor 4-α (HNF4-α); Liver; Kidney; Stomach; Glucocorticoids

Address correspondence to Dr. Moffat J. Nyirenda, Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Tel: +44-(0)131 242 9235; Fax: +44-(0)131 242 6779; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 14, pp. 345–359, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12718619643013
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Transcritpional Effects of S100B on Neuroblastoma Cells: Perturbation of Cholesterol Homeostasis and Interference on the Cell Cycle

C. Bernardini,*1 W. Lattanzi,*1 R. Businaro,† S. Leone,‡ V. Corvino,* G. Sorci,§ G. Lauro,‡ L. Fumagalli,† R. Donato,§ and F. Michetti*

*Institute of Anatomy and Cell Biology, Catholic University, Rome, Italy
†Department of Cardiovascular Sciences, University La Sapienza, Rome, Italy
‡Department of Biology, University Roma TRE, Rome, Italy
§Department of Experimental Medicine and Biochemical Sciences, Sect. Anatomy, University of Perugia, Perugia, Italy

S100B is a Ca2+ binding protein mainly secreted by astrocytes in the vertebrate brain that is considered a multifunctional cytokine and/or a damage-associated molecular pattern (DAMP) protein and a marker of brain injury and neurodegeneration when measured in different body fluids. It has been widely shown that this protein can exert diverse effects in neural cultures depending on its concentration, having detrimental effects at micromolar concentrations. The molecular mechanisms underlying this effect are still largely unknown. This study attempts to delineate the genome-wide gene expression analysis of the events associated with exposure to micromolar concentration of S100B in a human neuroblastoma cell line. In this experimental condition cells undergo a severe perturbation of lipid homeostasis along with cell cycle arrest. These mechanisms might reasonably mediate some aspects of the S100B-related detrimental effects of S100B, although obvious differences between mature neurons and neuroblastoma cells have to be considered.

Key words: Microarray; Cholesterol biosynthesis; Lipid homeostasis; Cell cycle

1These authors contributed equally to this work.
Address correspondence to Prof. Fabrizio Michetti, M.D., Institute of Anatomy and Cell Biology, Catholic University, L.go F. Vito, 1, 00168 Rome, Italy. Tel: +39 06 30155848; Fax: +39 06 30154813; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 14, pp. 361–370, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12735213181242
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Identification of a Gene Expression Signature for Survival Prediction in Type I Endometrial Carcinoma

Kristina Levan,* Karolina Partheen,* Lovisa Österberg,* Björn Olsson,† Ulla Delle,* Saskia Eklind,‡ and György Horvath*

*Department of Oncology, Sahlgrenska Hospital, Gothenburg University, Gothenburg, Sweden
†School of Life Sciences, University College of Skövde, Skövde, Sweden
‡Department of Obstetrics and Gynaecology, Sahlgrenska Hospital, Gothenburg University, Gothenburg, Sweden

Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.

Key words: Expression array; Survival; Endometrial cancer

Address correspondence to Kristina Levan, Department of Oncology, Göteborg University, Blå Stråket 2, 4th floor, SE-413 45 Gothenburg, Sweden. Tel: +46 31 324 78 55; Fax: +46 31 41 72 05; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it