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EP News—Section Editors: T. Jared Bunch, Penelope A. Boyden, N.A. Mark Estes III, Erica S. Zado| Volume 15, ISSUE 2, P311, February 01, 2018

EP News: Basic and Translational

Published:December 20, 2017DOI:https://doi.org/10.1016/j.hrthm.2017.12.002
      Despite success in directly reprogramming fibroblasts into cell types, the changes that occur as fibroblasts progressively convert to the target cell fates remain unclear. Liu et al (Nature 2017;551:100, PMID 29072293) used single-cell RNA sequencing to analyze global transcriptome changes at early stages during the reprogramming of mouse fibroblasts into induced cardiomyocytes (iCMs). Using unsupervised dimensionality reduction and clustering algorithms, they identified molecularly distinct subpopulations of cells during reprogramming. They constructed routes of iCM formation and delineated the relationship between cell proliferation and iCM induction. Analysis of the top candidate splicing factor, Ptbp1, revealed that it is a critical barrier for the acquisition of cardiomyocyte-specific splicing patterns in fibroblasts. Ptbp1 depletion promoted cardiac transcriptome acquisition and increased iCM reprogramming efficiency. The authors conclude that their single-cell transcriptomic approaches enabled them to reconstruct the reprogramming trajectory and uncover intermediate cell populations in iCM induction.
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