Pluto Bioinformatics

GSE149664: Generation of induced motor neurons (iMNs) from human fibroblasts facilitates locomotor recovery after spinal cord injury

Bulk RNA sequencing

Generation of autologous motor neurons holds a great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows the generation of target cell types from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic populations that are not readily scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequential induction of OCT4 and LHX3. Our strategy enables large production of pure iMNs through self-renewing iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited the hallmarks of spinal motor neurons including cellular morphology, marker expression, electrophysiological property, synaptic activity, and formation of neuromuscular junctions. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in SCI model. Taken together, our advanced strategy will provide tools to acquire sufficient iMNs that may represent a promising cell source for personalized cell therapy. SOURCE: Marcos,J,Araúzo-Bravo ( - Computational Biology and Bioinformatics Max Planck Institute for Molecular Biomedicine

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