Ichida JK, Staats KA, Davis-Dusenbery BN, Clement K, Galloway KE, Babos KN, Shi Y, Son EY, Kiskinis E, Atwater N, Gu H, Gnirke A, Meissner A, Eggan K. 2018. Comparative genomic analysis of embryonic, lineage-converted and stem cell-derived motor neurons. Development (Cambridge, England). 145(22). Pubmed: 30337375 DOI:10.1242/dev.168617


Advances in stem cell science allow the production of different cell types either through the recapitulation of developmental processes, often termed 'directed differentiation', or the forced expression of lineage-specific transcription factors. Although cells produced by both approaches are increasingly used in translational applications, their quantitative similarity to their primary counterparts remains largely unresolved. To investigate the similarity between -derived and primary cell types, we harvested and purified mouse spinal motor neurons and compared them with motor neurons produced by transcription factor-mediated lineage conversion of fibroblasts or directed differentiation of pluripotent stem cells. To enable unbiased analysis of these motor neuron types and their cells of origin, we then subjected them to whole transcriptome and DNA methylome analysis by RNA sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). Despite major differences in methodology, lineage conversion and directed differentiation both produce cells that closely approximate the primary motor neuron state. However, we identify differences in Fas signaling, the Hox code and synaptic gene expression between lineage-converted and directed differentiation motor neurons that affect their utility in translational studies.
© 2018. Published by The Company of Biologists Ltd.

Related Faculty

Photo of Kevin Eggan

Kevin Eggan investigates the mechanisms that cause motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS), and seeks to translate new discoveries into new therapeutic options for patients.

Photo of Alex Meissner

The Meissner laboratory uses genomic tools to study stem cell biology with a particular focus on epigenetic reprogramming.

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