eprintid: 10040279 rev_number: 35 eprint_status: archive userid: 608 dir: disk0/10/04/02/79 datestamp: 2017-12-19 11:11:11 lastmod: 2021-12-13 01:53:50 status_changed: 2017-12-19 11:11:11 type: article metadata_visibility: show creators_name: Schwartzentruber, J creators_name: Foskolou, S creators_name: Kilpinen, H creators_name: Rodrigues, J creators_name: Alasoo, K creators_name: Knights, AJ creators_name: Patel, M creators_name: Goncalves, A creators_name: Ferreira, R creators_name: Benn, CL creators_name: Wilbrey, A creators_name: Bictash, M creators_name: Impey, E creators_name: Cao, L creators_name: Lainez, S creators_name: Loucif, AJ creators_name: Whiting, PJ creators_name: Gutteridge, A creators_name: Gaffney, DJ creators_name: HIPSCI Consortium, title: Molecular and functional variation in iPSC-derived sensory neurons ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F85 divisions: D13 divisions: G23 keywords: Epigenomics, Gene expression, Gene regulation, Stem-cell research, Transcriptomics note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: Induced pluripotent stem cells (iPSCs), and cells derived from them, have become key tools for modeling biological processes, particularly in cell types that are difficult to obtain from living donors. Here we present a map of regulatory variants in iPSC-derived neurons, based on 123 differentiations of iPSCs to a sensory neuronal fate. Gene expression was more variable across cultures than in primary dorsal root ganglion, particularly for genes related to nervous system development. Using single-cell RNA-sequencing, we found that the number of neuronal versus contaminating cells was influenced by iPSC culture conditions before differentiation. Despite high differentiation-induced variability, our allele-specific method detected thousands of quantitative trait loci (QTLs) that influenced gene expression, chromatin accessibility, and RNA splicing. On the basis of these detected QTLs, we estimate that recall-by-genotype studies that use iPSC-derived cells will require cells from at least 20-80 individuals to detect the effects of regulatory variants with moderately large effect sizes. date: 2018 date_type: published official_url: https://doi.org/10.1038/s41588-017-0005-8 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1519120 doi: 10.1038/s41588-017-0005-8 pii: 10.1038/s41588-017-0005-8 lyricists_name: Bictash, Magda lyricists_name: Kilpinen, Leena Helena lyricists_name: Whiting, Paul lyricists_id: MBICT50 lyricists_id: HKILP03 lyricists_id: PWHIT17 actors_name: Whiting, Paul actors_id: PWHIT17 actors_role: owner full_text_status: public publication: Nature Genetics volume: 50 pagerange: 54-61 event_location: United States issn: 1546-1718 citation: Schwartzentruber, J; Foskolou, S; Kilpinen, H; Rodrigues, J; Alasoo, K; Knights, AJ; Patel, M; ... HIPSCI Consortium; + view all <#> Schwartzentruber, J; Foskolou, S; Kilpinen, H; Rodrigues, J; Alasoo, K; Knights, AJ; Patel, M; Goncalves, A; Ferreira, R; Benn, CL; Wilbrey, A; Bictash, M; Impey, E; Cao, L; Lainez, S; Loucif, AJ; Whiting, PJ; Gutteridge, A; Gaffney, DJ; HIPSCI Consortium; - view fewer <#> (2018) Molecular and functional variation in iPSC-derived sensory neurons. Nature Genetics , 50 pp. 54-61. 10.1038/s41588-017-0005-8 <https://doi.org/10.1038/s41588-017-0005-8>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10040279/1/C%3A%5CUsers%5CPaul%5CDocuments%5CPfizer%20legacy%5CGutteridge%20paper%5CSensory%20neurons-main%20paper.Resubmit.2017-8.pdf