Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes.
Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.
CECS, I-STEM (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases), AFM, Evry, France.
Yves
Y
Maury
CECS, I-STEM (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases), AFM, Evry, France.
Julien
J
Côme
CNRS UMR 8118, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
Rebecca A
RA
Piskorowski
INSERM/UEVE UMR 861, I-STEM, AFM, Evry, France.
Nouzha
N
Salah-Mohellibi
CNRS UMR 8118, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
Vivien
V
Chevaleyre
INSERM/UEVE UMR 861, I-STEM, AFM, Evry, France.
Marc
M
Peschanski
INSERM/UEVE UMR 861, I-STEM, AFM, Evry, France.
Cécile
C
Martinat
INSERM/UEVE UMR 861, I-STEM, AFM, Evry, France.
Stéphane
S
Nedelec
D002454:Cell Differentiation; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D009474:Neurons / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*