Deconstructing transcriptional heterogeneity in pluripotent stem cells
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Author
Kumar, Roshan M.
Shalek, Alex K.
Satija, Rahul
DaleyKeyser, AJay
Li, Hu
Pardee, Keith
Gennert, David
Trombetta, John J.
Regev, Aviv
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nature13920Metadata
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Kumar, R. M., P. Cahan, A. K. Shalek, R. Satija, A. DaleyKeyser, H. Li, J. Zhang, et al. 2014. “Deconstructing transcriptional heterogeneity in pluripotent stem cells.” Nature 516 (7529): 56-61. doi:10.1038/nature13920. http://dx.doi.org/10.1038/nature13920.Abstract
SUMMARY Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to characterize transcriptional heterogeneity in PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signaling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal, and a distinct chromatin state, an effect mediated by opposing miRNA families acting on the c-myc / Lin28 / let-7 axis. These data illuminate the nature of transcriptional heterogeneity in PSCs.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256722/pdf/Terms of Use
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