Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming

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• dc.contributor.author Francesconi, Mirko
• dc.contributor.author Di Stefano, Bruno, 1984-
• dc.contributor.author Berenguer, Clara
• dc.contributor.author de Andrés-Aguayo, Luisa
• dc.contributor.author Plana-Carmona, Marcos
• dc.contributor.author Mendez-Lago, Maria
• dc.contributor.author Guillaumet-Adkins, Amy
• dc.contributor.author Rodríguez Esteban, Gustavo
• dc.contributor.author Gut, Marta
• dc.contributor.author Gut, Ivo Glynne
• dc.contributor.author Heyn, Holger
• dc.contributor.author Lehner, Ben, 1978-
• dc.contributor.author Graf, T. (Thomas)
• dc.date.accessioned 2019-05-20T07:54:54Z
• dc.date.available 2019-05-20T07:54:54Z
• dc.date.issued 2019
• dc.description.abstract Forced transcription factor expression can transdifferentiate somatic cells into other specialised cell types or reprogram them into induced pluripotent stem cells (iPSCs) with variable efficiency. To better understand the heterogeneity of these processes, we used single-cell RNA sequencing to follow the transdifferentation of murine pre-B cells into macrophages as well as their reprogramming into iPSCs. Even in these highly efficient systems, there was substantial variation in the speed and path of fate conversion. We predicted and validated that these differences are inversely coupled and arise in the starting cell population, with Mychigh large pre-BII cells transdifferentiating slowly but reprogramming efficiently and Myclow small pre-BII cells transdifferentiating rapidly but failing to reprogram. Strikingly, differences in Myc activity predict the efficiency of reprogramming across a wide range of somatic cell types. These results illustrate how single cell expression and computational analyses can identify the origins of heterogeneity in cell fate conversion processes.
• dc.description.sponsorship We would like to thank Ido Amit and Diego Adhemar Jaitin for help with the MARS-Seq technique and the CRG/UPF FACS Unit for help with the cell sorting. Work in the lab of TG was supported by the European Research Council (ERC) Synergy Grant (4D-Genome) and by AGAUR (SGR-1136). Research in the lab of BL was supported by an ERC Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2011-26206), the AXA Research Fund, the Bettencourt Schueller Foundation and AGAUR (SGR-831). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013–2017 (SEV-2012–0208) and of the CERCA Programme/Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Francesconi M, Di Stefano B, Berenguer C, de Andrés-Aguayo L, Plana-Carmona M, Mendez-Lago M, Guillaumet-Adkins A, Rodriguez-Esteban G, Gut M, Gut IG, Heyn H, Lehner B, Graf T. Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming. Elife. 2019; 8. pii: e41627. DOI 10.7554/eLife.41627
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.41627
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/37247
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.ispartof Elife. 2019; 8. pii: e41627
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2011-26206
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
• dc.rights © Francesconi et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Computational biology
• dc.subject.keyword Mouse
• dc.subject.keyword Regenerative medicine
• dc.subject.keyword Reprogramming
• dc.subject.keyword Single cell
• dc.subject.keyword Stem cells
• dc.subject.keyword Systems biology
• dc.subject.keyword Transdifferentiation
• dc.title Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion