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Neural stem cell plasticity

Our team deciphers the mechanisms that control stem cell proliferation during development, childhood cancers and tissue regeneration. We mainly investigate these processes in the central nervous system.

Lorsque nous comprendrons parfaitement comment les cellules souches sont contrôlées dans notre corps, pourrons-nous régénérer les organes blessés ou guérir les cancers ?

Notre laboratoire combine deux des organismes modèles les plus puissants (la drosophile et l’embryon aviaire) avec de nouvelles technologies pour manipuler et étudier les cellules souches neurales avec une précision moléculaire sans précédent. Cela nous permet de déchiffrer les différents niveaux de régulation contrôlant le déroulement des programmes génétiques dans les cellules souches au cours du développement normal, de la régénération et dans les cancers ayant des origines développementales comme les cancers pédiatriques.

Nous étudions comment les cellules souches sont contrôlées par l’épigénétique, la transcription et la traduction, mais aussi par les signaux biochimiques et mécaniques produits par leur environnement.
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of the team

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They drive our research
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Alumni

They contributed to our research
Cassandra Gaultier
Scientifique à Abcam, Cambridge
Sara Genovese
Conseillère scientifique chez CTI Biopharma
Caroline Dillard
Chercheuse senior, Hôpital Universitaire d'Oslo

Funding bodies

They support our research
ARN
La ligue contre le cancer
CENTURI
Fondation Recherche Medicale

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Neural stem cell plasticity

We are currently developing several lines of research:

Temporal regulation of neural stem cell proliferative properties

One of our main goals is to understand how the progression of developmental programs is promoted in neural stem cells to modulate their proliferative properties during the course of Drosophila development. We look at chromatin and transcriptional dynamics using approaches such as single-cell ATAC-seq & RNA-seq. We are also interested in deciphering the post-transcriptional control of neural stem cell properties. For this purpose, we use proteomics and are developing new technologies (in collaboration with the lab of Harold Cremer) to profile microRNAs in specific cell-types.

Using the avian embryo, we also investigate how cellular mechanics may interfere or direct the temporal progression of developmental programs in neural stem cells. Such studies involve using transgenic quail lines, live imaging of the developing neural tube, and gene manipulation in the chick embryo using CRISPR/Cas9.

Deconstructing the principles of cellular hierarchy in neural stem cell tumors with a developmental origin

It has been proposed that cancers in children are caused by tumors composed of cells that are “locked” in their developmental programs. A large part of the team is dedicated to understanding how developmental programs may be coopted during development to promote tumorigenesis and govern the cellular hierarchy of tumors. We do most of our work in a Drosophila model of brain tumors. Deciphering the underlying principles involves combining the unmatched genetic tools available in Drosophila with single-cell multi-omics approaches, but also live-imaging of tumors, deep-learning based image analysis and computer simulations.

Recently, we have started to use the avian embryo as a model to investigate the initiation of pediatric tumors in a vertebrate animal model. The avian embryo offers the advantage of an easy access to early developmental stages for gain and loss fonction experiments, and live imaging. Eggs are cheap and are widely available all year long. In addition, working with the avian embryo only raises limited ethical concerns.

Regulation of gene expression during differentiation upon asymmetric divisions of neural stem cells

Using in vivo AGO-APP, a new strategy developed in collaboration with the Cremer lab, we are investigating how the dynamic expression of microRNAs contributes to staging the different steps of neuronal maturation, in coordination with the developmental progression of the organism. We are also interested in how chromatin becomes reorganized during the process of neuronal maturation.

Regulation of developmental programs by the steroid hormone ecdysone

Pulses of ecdysone produced during Drosophila development provide temporal signals that promote progression of developmental programs and limit regenerative potential. However, the mode of action of ecdysone is still not fully understood. Using RNA-seq, ATAC-seq and Cut & Run approaches, we investigate how ecdysone cooperates with various types of transcription factors to modulate chromatin structure and promote the unfolding of developmental programs, from stem cell self-renewal to terminal differentiation.