Ecole doctorale "LOGIQUE DU VIVANT

Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et prénom du directeur de thèse (et si besoin du co-directeur) :
Shahragim TAJBAKHSH
Le directeur de thèse et le co-directeur doivent impérativement être habilités à diriger les recherches (HDR)
Coordonnées
Tel : 01 40 61 35 20
e-mail : [email protected]
Nom et prénom du co-encadrant (non HdR ) (s’il y a lieu) :
Coordonnées Tel :
e mail
Nom et prénom du responsable de l’équipe : Shahragim TAJBAKHSH
Nombre de chercheurs et enseignants-chercheurs statutaires de l’équipe titulaires d’une HDR : 2
Nom et prénom du responsable du laboratoire : Shahragim TAJBAKHSH
Intitulé du laboratoire et N° d’unité : Unité de Cellules Souches et Développement, URA 3738
Institut Pasteur, 25 rue du Docteur Roux – 75015 Paris
Spécialité :
Biologie cellulaire, Biologie du développement
Titre du projet de thèse :
Asymmetric cell divisions in skeletal muscle stem cells
Résumé du projet de thèse (1 page maximum, en anglais)
Stem cells are present in all tissues and organs, and are crucial for normal regulated growth and regeneration. In spite of
many advances in the field of stem cell biology, our understanding of stem cells properties and the regulation of their fate
remains limited. In this project skeletal muscle stem/progenitor cells will be investigated using mouse genetics, cell and
molecular biology and imaging approaches.
A major regenerative cell type in adult skeletal muscle is the satellite cell. Reports that some satellite cells may be more
'stem-like" has highlighted the heterogeneity of this population. The paired/homeobox genes Pax3 and Pax7, as well as the
myogenic factors Myf5, Myod, Mrf4 and Myogenin play important roles in regulating the establishement of skeletal muscle
from stem and progenitor cells in the embryo. During adult myogenesis, Pax7 and the myogenic regulators Myf5 and Myod
play important roles in self-renewal and lineage progression. In the laboratory, we have developed unique genetically
modified mice, in particular a transgenic Tg: Pax7-nGFP mouse to investigate how cell relationships in the lineage are
established and how this tissue is built.
Our previous studies showed that satellite cells can perform asymmetric cell divisions. Notably, co-segregation of template
DNA strands takes place to one daughter cell in vivo and in vitro. We have extended these studies and identified a
subpopulation of satellite cells that performs non-random DNA segregation as well as asymmetric distribution of
transcription factors during cell division. The project will involve the detailed characterisation of asymmtric cell divisions
and its impact on regeneration, its relation to the stem cell properties, and cell fate decisions. Satellite cells will be also
studied in their quiescent state where a novel dormant cell state was identified in our laboratory. The characterisation of
muscle stem cells will provide valuable information about stem cells in general and their genetic and epigenetic regulation
as well as contributing to how organogenesis and regeneration are regulated in young and aged mice.
References:
Shinin, V., Gayraud-Morel, B., Gomes, D., and Tajbakhsh, S. (2006). Asymmetric division and cosegregation of
template DNA strands in adult muscle satellite cells. Nat Cell Biol 8, 677-82.
Cossu G, Tajbakhsh S. (2007). Oriented cell divisions and muscle satellite cell heterogeneity. Cell 129(5):859-61.
Tajbakhsh, S. (2009). Stem cell: what's in a name? Nature Reports Stem Cells. June 25.
Tajbakhsh, S., Rocheteau, P., Le Roux, I.. (2009). Asymmetric cell divisions and asymmetric cell fates. Annual Reviews
in Cell & Developmental Biology. 25:671-99.
Tajbakhsh, S. Gonzales, C. (2009). Biased segregation of DNA and centrosomes: moving together or drifting apart? Nature
Reviews Molecular & Cellular Biology 10: 804-810.
Rocheteau, P., Gayraud-Morel, B., Siegl-Cachedenier, I., Blasco, M. and S. Tajbakhsh (2012). A subpopulation of adult
skeletal muscle stem cells retains all template DNA strands after cell division. Cell, 48: 112-125.
Thèses actuellement en cours dans l’équipe
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et Prénom du doctorant
Francesca Pala
Meryem Baghdadi
Nom du directeur de thèse
Année de 1ere
inscription et
Ecole Doctorale
Shahragim TAJBAKHSH
Shahragim TAJBAKHSH
Oct 2013
Oct 2013
Financement pendant la thèse
Institut Pasteur PPU
Paris 6 UPMC/ Ministère
Trois publications récentes du directeur de thèse (du co-directeur ou du co-encadrant s’il y a lieu).Mettre en gras le nom
du directeur de thèse.
Gopalakrishnan, Swetha, Glenda Comai, Ramkumar Sambasivan, Alexandre Francou, Robert G Kelly, and Shahragim
Tajbakhsh. “A Cranial Mesoderm Origin for Esophagus Striated Muscles..” Developmental Cell 34, no. 6 (September 28,
2015): 694–704. doi:10.1016/j.devcel.2015.07.003.
Le Roux, Isabelle, Julie Konge, Laurent Le Cam, Patricia Flamant, and Shahragim Tajbakhsh. “Numb Is Required to
Prevent P53-Dependent Senescence Following Skeletal Muscle Injury.” Nature Communications 6 (2015): 8528.
doi:10.1038/ncomms9528.
Comai, Glenda, Ramkumar Sambasivan, Swetha Gopalakrishnan, and Shahragim Tajbakhsh. “Variations in the Efficiency
of Lineage Marking and Ablation Confound Distinctions Between Myogenic Cell Populations..” Developmental Cell 31, no.
5 (December 8, 2014): 654–67. doi:10.1016/j.devcel.2014.11.005.
Docteurs encadrés par le directeur de thèse ayant soutenu après septembre 2010 et publications relatives à leur sujet de thèse.
Mettre en gras le nom du directeur de thèse et celui du docteur.
Nom Prénom : Pierre Rocheteau
Date de soutenance : 10 février 2010
Durée de thèse (en mois): 42 mois
Ecole Doctorale : CdV
Publications :
Rocheteau, P. and S. Tajbakhsh (2008). ADN Immortel ou signature épigénétique? Médecine/Sciences, 24: 847-852.
Jory, A., Le Roux, I., Gayraud-Morel, B., Rocheteau, P, Cohen-Tannoudji, M., Cumano, A. and S. Tajbakhsh.
(2009). Numb promotes progenitor cell self-renewal in the embryonic somite. Stem Cells. 27: 2769-2780.
Tajbakhsh, S., Rocheteau, P., Le Roux, I.. (2009). Asymmetric cell divisions and asymmetric cell fates. Annual
Reviews in Cell & Developmental Biology. 25:671-99
Rocheteau, P., Gayraud-Morel, B., Siegl-Cachedenier, I., Blasco, M. and S. Tajbakhsh (2012). A subpopulation of
adult skeletal muscle stem cells retains all template DNA strands after cell division. Cell, 48: 112-125.
Mourikis, P. R. Sambasivan, D. Castel, P. Rocheteau, V. Bizzarro and S. Tajbakhsh (2012). A critical requirement
for Notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells, 30: 243-252.
Lathil, M., P. Rocheteau, L. Châtre, S. Sanulli, S. Memet, M. Ricchetti, S. Tajbakhsh#, and F. Chrétien# (2012).
Skeletal muscle stem cells adopt a dormant state post mortem and retain regenerative capacity. Nature
Communications, June 12; 3: 903; # equal contributing authors
Nom Prénom : Siham Yennek
Date de soutenance : 25 septembre 2015
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Durée de thèse (en mois): 72 mois
Ecole Doctorale : CdV
Publications :
Yennek, S. and S. Tajbakhsh (2013). DNA asymmetry and cell fate regulation in stem cells. Seminars in Cell &
Developmental Biology, 8-9:627-642.
Yennek, S., M. Burute, M. Théry and S. Tajbakhsh (2014). Cell adhesion geometry regulates non-random DNA
segregation and asymmetric cell fates in mouse skeletal muscle stem cells. Cell Reports, 7:961-970.
Dentice M, Ambrosio R, Damiano V, Sibilio A, Luongo C, Guardiola O, Yennek S, Zordan P, Minchiotti G, Colao A,
Marsili A, Brunelli S, Del Vecchio L, Larsen PR, Tajbakhsh S, Salvatore D. (2014). Intracellular inactivation of
thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. Cell Metabolism
20:1038-48.
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