Comparative genomic analysis of embryonic, lineage-converted, and stem cell-derived motor neurons
Abstract
Advances in stem cell science allow the production of different cell types in vitro 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 in vitro-derived and primary cell types, we harvested and purified mouse spinal motor neurons and compared them to 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2018
- Source ID
- 10.1242/dev.168617
Entities
People
- Alexander Meissner
- Andreas Gnirke
- Brandi N. Davis-dusenbery
- Esther Y. Son
- Evangelos Kiskinis
- Hongcang Gu
- Justin K Ichida
- Kate E. Galloway
- Kendell Clement
- Kevin Eggan
- Kim A. Staats
- Kimberly N. Babos
- Nicholas Atwater
- Yingxiao Shi
Organizations
- Broad Institute
- Harvard University
- Howard Hughes Medical Institute
- Max Planck Institute for Molecular Genetics
- National Institutes of Health
- United States Department of Defense
- University of Southern California