Francesconi, MirkoDi Stefano, Bruno, 1984-Berenguer, Clarade Andrés-Aguayo, LuisaPlana-Carmona, MarcosMendez-Lago, MariaGuillaumet-Adkins, AmyRodríguez Esteban, GustavoGut, MartaGut, Ivo GlynneHeyn, HolgerLehner, Ben, 1978-Graf, T. (Thomas)2019-05-202019-05-202019Francesconi 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.416272050-084Xhttp://hdl.handle.net/10230/37247Forced 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.41627Computational biologyMouseRegenerative medicineReprogrammingSingle cellStem cellsSystems biologyTransdifferentiationinfo:eu-repo/semantics/openAccess