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

Ichida, J. K., Staats, K. A., Davis-Dusenbery, B. N., Clement, K., Galloway, K. E., Babos, K. N., et al. (2018). Comparative genomic analysis of embryonic, lineage-converted and stem cell-derived motor neurons. Development, 145(22): pii: dev168617. doi:10.1242/dev.168617.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4D4F-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4D50-D
Genre: Journal Article

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 Creators:
Ichida, Justin K. , Author
Staats, Kim A. , Author
Davis-Dusenbery, Brandi N. , Author
Clement, Kendell , Author
Galloway, Kate E. , Author
Babos, Kimberly N. , Author
Shi, Yingxiao , Author
Son, Esther Y. , Author
Kiskinis, Evangelos , Author
Atwater, Nicholas , Author
Gu, Hongcang , Author
Gnirke, Andreas , Author
Meissner, Alexander1, 2, 3, Author              
Eggan, Kevin , Author
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA , ou_persistent22              
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, ou_persistent22              

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Free keywords: Directed differentiation; Embryonic stem cells; Lineage conversion; Motor neuron; Reprogramming; iPS cell
 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 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.

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Language(s): eng - English
 Dates: 2018-10-152018-11-21
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1242/dev.168617
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Title: Development
  Other : Development
Source Genre: Journal
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Publ. Info: Cambridge, Cambridgeshire : Company of Biologists
Pages: - Volume / Issue: 145 (22) Sequence Number: pii: dev168617 Start / End Page: - Identifier: ISSN: 0950-1991 (print)
ISSN: 1477-9129 (online)
CoNE: https://pure.mpg.de/cone/journals/resource/954927546241