Nedelec

News

The work of Vincent and Célia was recently published (https://dev.biologists.org/content/148/6/dev194514). It was featured in a research highlight (https://dev.biologists.org/content/148/6/e0603) and in a “people behind the paper” interview (https://dev.biologists.org/content/148/6/dev199579).

One consequence of this work is the ability to efficiently generate spinal neuronal subtypes for basic research and disease modeling. If you’re interested contact us.

Research

Our lab is studying the molecular and cellular basis of human development in health and disease. To approach this question we use human pluripotent stem cell differentiation into organoids or specific cell types coupled to transcriptomic, optogenetic and live imaging approaches

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We seek to decode the principles controlling the specification and organization of neural diversity and how genetic mutations perturb these events to cause disorders. To approach these questions, we are creating in vitro models of human embryogenesis based on the differentiation human induced pluripotent stem cells. These models are not only revolutionizing the way we address the mechanisms controlling the formation of organs and specific cell types, but also open avenues to produce defined cell populations or tissues (cell and tissue engineering) to study disease mechanims, for cell therapy strategies (transplantation) or drug screening.

Synthetic human developmental biology for basic research, cell and tissue engineering

1) Using targeted differentiation of human pluripotent stem cells toward specific neuronal subtypes, we investigate the signal transduction pathways and genetic networks that ensure the formation of distinct locomotor neural circuits along the body axis. (Projects of Célia Vaslin and Rémi Robert, see also Nedelec, Martinez-Arias, Cur. Op. Neuro, 2021). Building on our previous work in which we invented a new way to investigate cell fate control using in vitro differentiation of human pluripotent stem cells (Maury et al. Nature Biotechnology, 2015), we have recently discovered mechanisms reguling HOX gene expression resulting in the first efficient methods to generate distinct motor neuron subtypes differentially impacted in motor neuron diseases (Mouilleau, Vaslin et al, Development, 2021).

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2) Using organoid differentiation, we study the coupling between the morphogenesis of the neural tube and the spatial allocation of specific neuronal circuits (Project of Simona Gribaudo). We are finalizing a manuscript reporting a new type of spinal organoids and wish to recruit a student or a post-doc to follow up on this project.

Synthetic human developmental biology for disease modeling

These in vitro models provide access to human tissues or cell types affected in pathologies. We use patient-derived induced pluripotent stem cells to study the basis of motor neuron diseases, a heterogeneous group of incurable and often fatal diseases. In particular, we are studying infantile spinal muscular atrophies (SMAs) which, although caused by mutations in ubiquitously expressed genes, are characterized by defects in the formation or survival of particular populations of motor neurons while others are preserved. Deciphering the basis of the vulnerability or the resistance of these different types of motor neurons should open new therapeutic avenues (Maeliss Calon’s project).

Using these new in vitro models, we will soon start a project funded by FRM on the molecular and cellular basis of a juvenile form of amyotrophic lateral sclerosis. (Collaboration with Odil Porrua, IJM, Paris)

Methods

• Human induced pluripotent stem cell (iPS)
• organoid
• Transcriptomics
• Microfluidic
• Histology
• Live imaging

People

Team leader : Stéphane NEDELEC CR1 INSERM

• Simona Gribaudo, Research engineer, Sorbonne Université
• Célia Vaslin, PhD student
• Rémi Robert, PhD student (Cosupervised with J. van Helden, ATGC, Marseille)
• Maeliss Calon, PhD student (Cosupervised with A. Baffet, Curie Institute)
• Mathieu Daynac, Post doctoral scientist

Collaborators

• V. Ribes, IJM, Paris
• A. Baffet, Curie Institute, Paris
• N. Bahi-Buisson, Imagine Institute, Paris
• X. Morin, ENS, Paris
• A. Rossor, UCL, London
• E. Mazzoni, NYU, New York,
• H. Wichterle, Columbia University, New York
• M. Coppey, Curie institute, Paris
• B. Sorre, Curie institute, Paris
• C. Villard, IPGG, Paris
• O. Porrua-Fuerte, IJM, Paris

Funding

• ATIP/Avenir program – Inserm
• Association Francaise contre les Myopathies (AFM)
• Agence Nationale de la Recherche (ANR)
• Fondation pour la Recherche Médicale (FRM)
• Fondation maladies rares