In vitro myelin formation using embryonic stem cells

Author:

Kerman Bilal E.1,Kim Hyung Joon1,Padmanabhan Krishnan123,Mei Arianna1,Georges Shereen1,Joens Matthew S.4,Fitzpatrick James A. J.4,Jappelli Roberto1,Chandross Karen J.5,August Paul6,Gage Fred H.1

Affiliation:

1. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

2. Computational Neuroscience Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

3. Crick Jacobs Center for Theoretical and Computational Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

4. Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

5. Sanofi US, R&D, Genzyme MS/Neurology, 55 Corporate Drive, Bridgewater, NJ 08807, USA

6. Sanofi US, R&D, Early to Candidate Unit, Tucson Innovation Center, 2090 E. Innovation Park Drive, Tucson, AZ 85755, USA

Abstract

Myelination in the central nervous system is the process by which oligodendrocytes form myelin sheaths around the axons of neurons. Myelination enables neurons to transmit information more quickly and more efficiently and allows for more complex brain functions; yet, remarkably, the underlying mechanism by which myelination occurs is still not fully understood. A reliable in vitro assay is essential to dissect oligodendrocyte and myelin biology. Hence, we developed a protocol to generate myelinating oligodendrocytes from mouse embryonic stem cells and established a myelin formation assay with embryonic stem cell-derived neurons in microfluidic devices. Myelin formation was quantified using a custom semi-automated method that is suitable for larger scale analysis. Finally, early myelination was followed in real time over several days and the results have led us to propose a new model for myelin formation.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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