Microhexagon gradient array directs spatial diversification of spinal motor neurons

Theranostics
Geok Soon LimHuilin Shao

Abstract

Motor neuron diversification and regionalization are important hallmarks of spinal cord development and rely on fine spatiotemporal release of molecular cues. Here, we present a dedicated platform to engineer complex molecular profiles for directed neuronal differentiation. Methods: The technology, termed microhexagon interlace for generation of versatile and fine gradients (microHIVE), leverages on an interlocking honeycomb lattice of microstructures to dynamically pattern molecular profiles at a high spatial resolution. By packing the microhexagons as a divergent, mirrored array, the platform not only enables maximal mixing efficiency but also maintains a small device footprint. Results: Employing the microHIVE platform, we developed optimized profiles of growth factors to induce rostral-caudal patterning of spinal motor neurons, and directed stem cell differentiation in situ into a spatial continuum of different motor neuron subtypes. Conclusions: The differentiated cells showed progressive RNA and protein signatures, consistent with that of representative brachial, thoracic and lumbar regions of the human spinal cord. The microHIVE platform can thus be utilized to develop advanced biomimetic systems for the study of disease...Continue Reading

Citations

May 16, 2019·Neural Regeneration Research·UNKNOWN WinantoShi-Yan Ng
Jun 5, 2020·Science Advances·Xingjie WuHuilin Shao
Jul 28, 2019·Biomedical Microdevices·Sam ParittotokkapornSimon J O'Carroll
Oct 31, 2020·Trends in Molecular Medicine·Svetlana Pasteuning-VuhmanR Jeroen Pasterkamp

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Methods Mentioned

BETA
chip
dissection
profiler
PCR
Illumina sequencing

Software Mentioned

Solidworks
ImageJ
Comsol Multiphysics
FastQC
GraphPad Prism
Comsol
DESeq2
R
STAR aligner
microHIVE

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