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| '''Functional Genomics of the Human Embryo'''
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| == How to reach us == | | {|cellspacing="5" cellpadding="10" style="background:#000; width: 750px;" |
| Equipe Avenir (Etchevers)
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| INSERM U781, Tour Lavoisier, 2ème étage
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| Hôpital Necker - Enfants Malades
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| 149, rue de Sèvres
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| 75743 Paris Cedex 15
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| France
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| tel: (+33) 1 44 49 40 00 poste 97838
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| fax: (+33) 1 44 49 51 50
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| [http://www.necker.fr/irnem/Avenir.htm External web page with phone extensions]
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| | == Embryological bases of congenital malformations == |
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| <h3>Lab members</h3>
| | We are a small group of scientists working on human neural crest stem cells and their differentiated progeny in the head and thoracic region. Read all about it, and us, using the links above. |
| • [[User:Etchevers|Heather Corbett Etchevers]] <br>
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| • [[User:Thomas|Sophie Thomas]]<br>
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| • [[User:Golzio|Christelle Golzio ]]<br>
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| • [[User:Baala|Lekbir Baala ]]<br>
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| • [[User:Goudefroye|Geraldine Goudefroye ]]<br>
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| • [[User:Detrait|Eric Detrait]]<br>
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| • Equipe #2 of INSERM U781, Handicaps Génétiques de l'Enfant<br>
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| • Visitors<br>
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| | Like nested dolls, our group was, until July, 2010, part of [http://www.necker.fr/u781/Team_1.html a larger team] interested in the genetic bases of congenital diseases and malformations. That team, with some of our original members, remains part of the [http://www.necker.fr/u781 research unit #781], dedicated to "Genetics and Epigenetics of Neurometabolic Diseases and Birth Defects" (also [http://www.necker.fr/irnem/units/detail.php?id=8 see here]). |
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| <h3>Local techniques</h3>
| | I am developing new subtopics and accepting students within the [http://www.zaffranlab.com/ Genetics, patterning and cardiovascular diseases] group, which is part of the [http://umr910.timone.univ-mrs.fr/ Unité Mixte de Recherche 910] (with contributions from the [http://www.univmed.fr/fr/faculte-medecine Université Aix-Marseille II]) in Marseille. |
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| | We are all, nonetheless, part of the French equivalent to the intramural program of the U.S. [http://www.nih.gov/ N.I.H.], the Institut national de la santé et de la recherche médicale ([http://www.inserm.fr/ INSERM]). |
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| <h3>Trucs utiles</h3>
| | (Links out updated May 7, 2012.) |
| • Comment envoyer un Fedex<br>
| | *'''[[User:Etchevers|Heather]] 10:01, 7 May 2012 (EDT)''': |
| • Paperasse autour de la radioactivité<br>
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| == Research ==
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| === Human neural crest cell differentiation ===
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| Our current project concerns the transcriptional and phenotypic characterization of highly multipotent neural crest cells (NCC) derived from human embryos. Such characterization is a prerequisite to developing cell-based replacement therapies for congenital malformations or progressive diseases in which neural crest-derived lineages play a primary pathogenic role (“neurocristopathies”). Given their endogenous plasticity and shared heritage with neural stem cells, clinical applications for neural crest cells may prove to be even wider.
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| A quantitative SAGE analysis of the entire set of mRNA transcripts derived from primary human NCC is currently underway in our laboratory, in order to establish an initial transcriptional profile of genes that distinguish the undifferentiated state for this cell type. The SAGE data will be supplemented with that from a different functional genomics tool that is being exploited in our parent research group in the INSERM U781 and with our collaborators at Institut Curie, custom and standardized Affymetrix DNA microarrays. Statistical analysis and comparison of the SAGE and microarray results using bioinformatics should permit us to class transcripts into functional clusters and identify groups of genes that are up- or down-regulated during NCC differentiation.
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| In order to rapidly assess gene function, our group looks at the expression of candidate genes for certain neurocristopathies during normal human embryonic development using in situ hybridization on sections. We can also test the effects of gain or loss of gene function by targeting the NCC of the chicken embryo (a model with many technical advantages) using electroporation, and performing short- and long-term analyses.
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| Over the long term, our group also plans to immortalize human NCC shortly after their initial migration, when they most resemble “true” stem cells in their potential. We will test the capacity of the cells to differentiate appropriately after transplantation in vivo into the developing chicken embryo. In this way, we can define the capacity of multipotent NCC to acquire diverse cell phenotypes in an appropriate environment. We also intend to carry out in vitro characterizations under varying culture conditions and compare the properties of transformed versus primary human cells.
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| === Différenciation de la crête neurale humaine ===
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| '' Notre projet concerne la caractérisation transcriptionnelle et phénotypique des cellules multipotentes de la crête neurale (CN) dérivée d’embryons humains. Cette recherche est indispensable avant d’envisager de développer des cytothérapies de remplacement pour des « neurocristopathies » congénitales ou progressives tels le syndrome de Hirschsprung ou certaines neuropathies périphériques. Vu la plasticité endogène de la CN et ses caractéristiques partagées avec les cellules souches neuronales, les applications cliniques pourraient s’avérer encore plus larges.''
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| '' Nous entreprenons d’immortaliser des lignées de CN humaine peu de temps après la migration initiale de ces cellules, quand ils ont le plus grand potentiel de différenciation. Nous allons tester la capacité des lignées de se différencier correctement in vivo chez l’embryon de poulet. Une analyse quantitative SAGE du transcriptome entier des cellules CN humaines est en cours actuellement, afin d’établir le profil des gènes qui caractérisent l’état indifférencié de la CN.''
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| '' Ensuite, nous corroborons ces résultats avec un autre outil de génomique fonctionnel, des puces Affymetrix fait sur mesure ou standards, utilisés par nos collaborateurs de l’équipe au sens plus large de l’INSERM U781 et à l’Institut Curie. Nous comparerons par exemple le profil transcriptionnel des ganglions fœtaux avec celui de leurs précurseurs multipotents. Une analyse statistique et une comparaison bio-informatique des résultats SAGE et microarray devrait nous permettre de classer les transcrits par groupes fonctionnels qui sont modulés au cours de la différenciation.'' | |
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| '' Afin d’évaluer rapidement la fonction de tels groupes, nous examinerons l’expression de gènes candidats pour des neurocristopathies humaines par l’hybridation in situ sur des coupes d’embryons humains normaux. Nous effectuerons aussi des gains ou pertes de fonction de ces gènes au sein de la CN de l’embryon de poulet afin de voir l’effet sur sa différenciation dans un environnement approprié. Ainsi, nous espérons identifier des nouveaux gènes responsables de neurocristopathies ainsi que de connaître leurs modes de fonctionnement qui pourront mener à des voies thérapeutiques.''
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| --[[User:Etchevers|Alethea]] 04:11, 24 January 2006 (EST)
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