Stem cells in neurodevelopment and diseases
Research
In the nervous system, the specification of hundreds of distinct neuronal subtypes during embryonic development underlies the formation of neural circuits encoding cognitive functions and behaviors. Functional impairments or degeneration of specific neuronal populations underpin most neurological disorders. The links between neuronal diversity and the selectivity of neurodegenerative diseases remain elusive. To approach this question, we are using human induced pluripotent stem cells, mouse embryonic stem cells and embryology approaches to decipher the complex cross talks of developmental cues that control the specification of neuronal subtypes in the spinal cord, hindbrain and cortex and assess the differential vulnerability of specific neuronal subtypes in diseases such as spinal muscular atrophies.
Methods
- Human induced pluripotent stem cell (iPS)
- Mouse embryonic stem cell (ES)
- Large scale targeted differentiation of pluripotent stem cells
- Transcriptomics
- Microfluidic
- Histology
People
Team leader : Stéphane NEDELEC CR1 INSERM
- Angélique Terray, IR, UPMC Nicolas Jardin,
- Post doctoral scientist
- Vincent Mouilleau, PhD student, (Cosupervised by Cécile Martina, Istem, Evry)
- Célia Vaslin, 2nd year Master Student
Direct Readout of Neural Stem Cell Transgenesis with an Integration-Coupled Gene Expression Switch.
Takuma Kumamoto, Franck Maurinot, Raphaëlle Barry-Martinet, Célia Vaslin, Sandrine Vandormael-Pournin, Mickaël Le, Marion Lerat, Dragos Niculescu, Michel Cohen-Tannoudji, Alexandra Rebsam, Karine Loulier, Stéphane Nedelec, Samuel Tozer, Jean Livet
Neuron. 2020 Jun 17;S0896-6273(20)30407-4.
PMID:32559415 
BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids.
Duval N, Vaslin C, Barata TC, Frarma Y, Contremoulins V, Baudin X, Nedelec S, Ribes VC.
Development. 2019 Jul 25;146(14). pii: dev175430.
PMID:31239243
Serotonin neurons in a dish.
Patricia Gaspar, Stéphane Nedelec
Nat Biotechnol. 2016 Jan;34(1):41-2.
PMID:26744978
Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes.
Yves Maury, Julien Côme, Rebecca A Piskorowski, Nouzha Salah-Mohellibi, Vivien Chevaleyre, Marc Peschanski, Cécile Martinat, Stéphane Nedelec
Nat Biotechnol. 2015 Jan;33(1):89-96.
PMID:25383599
Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity.
Esteban O Mazzoni, Shaun Mahony, Michael Closser, Carolyn A Morrison, Stephane Nedelec, Damian J Williams, Disi An, David K Gifford, Hynek Wichterle
Nat Neurosci. 2013 Sep;16(9):1219-27.
PMID:23872598
Genetically-modified human pluripotent stem cells: new hopes for the understanding and the treatment of neurological diseases?
Stéphane Nedelec, Brigitte Onteniente, Marc Peschanski, Cécile Martinat
Curr Gene Ther. 2013 Apr;13(2):111-9.
PMID:23444870
Concentration-dependent requirement for local protein synthesis in motor neuron subtype-specific response to axon guidance cues.
Stéphane Nédelec, Mirza Peljto, Peng Shi, Mackenzie W Amoroso, Lance C Kam, Hynek Wichterle
J Neurosci. 2012 Jan 25;32(4):1496-506.
PMID:22279234
An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming.
Mathieu Gabut, Payman Samavarchi-Tehrani, Xinchen Wang, Valentina Slobodeniuc, Dave O’Hanlon, Hoon-Ki Sung, Manuel Alvarez, Shaheynoor Talukder, Qun Pan, Esteban O Mazzoni, Stephane Nedelec, Hynek Wichterle, Knut Woltjen, Timothy R Hughes, Peter W Zandstra, Andras Nagy, Jeffrey L Wrana, Benjamin J Blencowe
Cell. 2011 Sep 30;147(1):132-46.
PMID:21924763
Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding.
Peng Shi, Stephane Nedelec, Hynek Wichterle, Lance C Kam
Lab Chip. 2010 Apr 21;10(8):1005-10.
PMID:20358107
Xenotransplantation of embryonic stem cell-derived motor neurons into the developing chick spinal cord.
Hynek Wichterle, Mirza Peljto, Stephane Nedelec
Methods Mol Biol. 2009;482:171-83.
PMID:19089356
