UCAGenomiX related publications

Du to our strong expertise in "omics" experiments and in microRNAs topics we decided to separate into 3 categories the related publications into which the Functional genomics Platform of Nice-Sophia-Antipolis is involved :
  1. Expression studies (DNA microarrays and high-throughput sequencing experiments)
  2. MicroRNA studies
  3. Miscellaneous

Dayem Manal

 dayem@ipmc.cnrs.fr
 04 93 95 77 92
 660 route des lucioles 06560 Valbonne - Sophia-Antipolis

4 publications found

1. Transcriptional signature of epidermal keratinocytes subjected to in vitro scratch wounding, reveals selective roles for ERK1/2, P38 and PI3K signalling pathways.
J Biol Chem. 2007 May 18;282(20):15090-102.
Fitsialos G, Chassot AA, Turchi L, Dayem MA, Lebrigand K, Moreilhon C, Meneguzzi G, Busca R, Mari B, Barbry P, Ponzio G
Faculte de Medecine, INSERM U634, Nice 06107.

Covering denuded dermal surfaces after injury requires migration, proliferation and differentiation of skin keratinocytes. To clarify the major traits controlling these intermingled biological events, we surveyed the genomic modifications occurring during the course of a scratch wound closure of cultured human keratinocytes. Using a DNA microarray approach, we report the identification of 161 new markers of epidermal repair. Expression data, combined with functional analysis performed with specific inhibitors of ERK, p38[MAPK] and PI3 kinases, demonstrate that kinase pathways exert very selective functions by precisely controlling the expression of specific genes. Inhibition of the ERK pathway totally blocks the wound closure and inactivates many early transcription factors and EGF-type growth factors. P38[MAPK] inhibition only delays "healing", probably in line with the control of genes involved in the propagation of injury-initiated signalling. In contrast, PI3 kinase inhibition accelerates the scratch closure and potentiates the scratch-dependent stimulation of three genes related to epithelial cell transformation, namely HAS3, HBEGF and Ets1. Our results define in vitro human keratinocyte wound closure as a repair process resulting from a fine balance between positive signals controlled by ERK and p38[MAPK], and negative ones triggered by PI3 kinase. The perturbation of any of these pathways might lead to dysfunction in the healing process, similar to those observed in pathological wounding phenotypes, such as hypertrophic scars or keloids.
Pubmed link : 17363378

2. Coordinated regulation of genes for secretion in tobacco at late developmental stages: association with resistance against oomycetes.
Plant Physiol. 2004 Feb;134(2):858-70. Epub 2004 Feb 5.
Hugot K, Riviere MP, Moreilhon C, Dayem MA, Cozzitorto J, Arbiol G, Barbry P, Weiss C, Galiana E
Institut National de la Recherche Agronomique, Unite Interactions Plantes-Microorganismes, Villa Thuret, Boite postale 2078, F-06606 Antibes cedex, France.

Besides the systemic acquired resistance (SAR) induced in response to microbial stimulation, host plants may also acquire resistance to pathogens in response to endogenous stimuli associated with their own development. In tobacco (Nicotiana tabacum), the vegetative-to-flowering transition comes along with a susceptibility-to-resistance transition to the causal agent of black shank disease, the oomycete Phytophthora parasitica. This resistance affects infection effectiveness and hyphal expansion and is associated with extracellular accumulation of a cytotoxic activity that provokes in vitro cell death of P. parasitica zoospores. As a strategy to determine the extracellular events important for restriction of pathogen growth, we screened the tobacco genome for genes encoding secreted or membrane-bound proteins expressed in leaves of flowering plants. Using a signal sequence trap approach in yeast (Saccharomyces cerevisiae), 298 clones were selected that appear to encode for apoplastic, cell wall, or membrane-bound proteins involved in stress response, in plant defense, or in cell wall modifications. Microarray and northern-blot analyses revealed that, at late developmental stages, leaves were characterized by the coordinate up-regulation of genes involved in SAR and in peroxidative cross-linking of structural proteins to cell wall. This suggests the potential involvement of these genes in extracellular events that govern the expression of developmental resistance. The analysis of the influence of salicylic acid on mRNA accumulation also indicates a more complex network for regulation of gene expression at a later stage of tobacco development than during SAR. Further characterization of these genes will permit the formulation of hypotheses to explain resistance and to establish the connection with development.
Pubmed link : 14764907

3. Gene expression profiling of normal human pulmonary fibroblasts following coculture with non-small-cell lung cancer cells reveals alterations related to matrix degradation, angiogenesis, cell growth and survival.
Oncogene. 2003 Nov 20;22(52):8487-97.
Fromigue O, Louis K, Dayem M, Milanini J, Pages G, Tartare-Deckert S, Ponzio G, Hofman P, Barbry P, Auberger P, Mari B
INSERM U526, IFR50, Faculte de Medecine Pasteur, Nice, France.

Increasing evidence supports a major role for the microenvironment in carcinoma formation and progression. The influence of the stroma is partly mediated by signalling between epithelial tumor cells and neighboring fibroblasts. However, the molecular mechanisms underlying these interactions are largely unknown. To mimic the initial steps of invasive carcinoma in which tumor cells come in contact with normal stromal cells, we used a coculture model of non-small-cell lung cancer tumor cells and normal pulmonary fibroblasts. Using DNA filter arrays, we first analysed the overall modification of gene expression profile after a 24 h period of coculture. Next, we focused our interest on the transcriptome of the purified fibroblastic fraction of coculture using both DNA filter arrays and a laboratory-made DNA microarray. These experiments allowed the identification of a set of modulated genes coding for growth and survival factors, angiogenic factors, proteases and protease inhibitors, transmembrane receptors, kinases and transcription regulators that can potentially affect the regulation of matrix degradation, angiogenesis, invasion, cell growth and survival. This study represents to our knowledge the first attempt to dissect early global gene transcription occurring in a tumor-stroma coculture model and should help to understand better some of the molecular mechanisms involved in heterotypic signalling between epithelial tumor cells and fibroblasts.
Pubmed link : 14627989

4. Early gene expression in wounded human keratinocytes revealed by DNA microarray analysis.
Comp Funct Genomics. 2003;4(1):47-55.
Dayem MA, Moreilhon C, Turchi L, Magnone V, Christen R, Ponzio G, Barbry P
Laboratoire de Physiologie Genomique des Eucaryotes CNRS/UNSA UMR 6097 IPMC F-06560 Sophia Antipolis France.

WOUND HEALING INVOLVES SEVERAL STEPS: spreading of the cells, migration and proliferation. We have profiled gene expression during the early events of wound healing in normal human keratinocytes with a home-made DNA microarray containing about 1000 relevant human probes. An original wounding machine was used, that allows the wounding of up to 40% of the surface of a confluent monolayer of cultured cells grown on a Petri dish (compared with 5% with a classical 'scratch' method). The two aims of the present study were: (a) to validate a limited number of genes by comparing the expression levels obtained with this technique with those found in the literature; (b) to combine the use of the wounding machine with DNA microarray analysis for large-scale detection of the molecular events triggered during the early stages of the wound-healing process. The time-courses of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA) and the signal transducer and transcription activator STAT3, were consistent with previously published data. This suggests that our methodologies are able to perform quantitative measurement of gene expression. Transcripts encoding two zinc finger proteins, ZFP36 and ZNF161, and the tumour necrosis factor alpha-induced protein TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen-activated protein kinase (p38MAPK) in wound healing was shown after the inhibition of p38 by SB203580, but our results also suggest the existence of surrogate activating pathways.
Pubmed link : 18629100