Deconstructing transcriptional heterogeneity in pluripotent stem cells

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Deconstructing transcriptional heterogeneity in pluripotent stem cells

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Title: Deconstructing transcriptional heterogeneity in pluripotent stem cells
Author: Kumar, Roshan M.; Cahan, Patrick; Shalek, Alex K.; Satija, Rahul; DaleyKeyser, AJay; Li, Hu; Zhang, Jin; Pardee, Keith; Gennert, David; Trombetta, John J.; Ferrante, Thomas C.; Regev, Aviv; Daley, George Q.; Collins, James J.

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
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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.
Published Version: doi:10.1038/nature13920
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256722/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295753
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