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Development DOI:10.1242/dev.168617

Comparative genomic analysis of embryonic, lineage-converted and stem cell-derived motor neurons.

Publication TypeJournal Article
Year of Publication2018
AuthorsIchida, 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
Date Published2018 Nov 21
KeywordsAnimals, Cell Lineage, Embryo, Mammalian, Epigenesis, Genetic, Genomics, Mice, Inbred C57BL, Motor Neurons, Pluripotent Stem Cells, Transcription, Genetic

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.


Alternate JournalDevelopment
PubMed ID30337375
PubMed Central IDPMC6262794
Grant ListR01 GM096067 / GM / NIGMS NIH HHS / United States
P01 GM099117 / GM / NIGMS NIH HHS / United States
R01 NS097850 / NS / NINDS NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
R01 DC015530 / DC / NIDCD NIH HHS / United States
T32 DC009975 / DC / NIDCD NIH HHS / United States
R01 DA036898 / DA / NIDA NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
K99 NS077435 / NS / NINDS NIH HHS / United States
S10 OD021553 / OD / NIH HHS / United States
R00 NS077435 / NS / NINDS NIH HHS / United States