1. Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming.
- Author
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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, and Graf T
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, RNA-Seq, Signal Transduction, Single-Cell Analysis, Transcriptome, Cell Lineage, Cell Transdifferentiation, Cellular Reprogramming, Induced Pluripotent Stem Cells cytology, Precursor Cells, B-Lymphoid cytology
- 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 Myc
high 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., Competing Interests: MF, BD, CB, Ld, MP, MM, AG, GR, MG, IG, HH, BL, TG No competing interests declared, (© 2019, Francesconi et al.)- Published
- 2019
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