Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency
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Lander_Integrative analyses.pdf
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1.91 MB
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Author(s)
Cacchiarelli, Davide
Trapnell, Cole
Ziller, Michael J.
Soumillon, Magali
Cesana, Marcella
Karnik, Rahul
Donaghey, Julie
Smith, Zachary D.
Ratanasirintrawoot, Sutheera
Zhang, Xiaolan
Date Issued
July 2015
Journal
Cell
Publisher
Elsevier
Citation
Cacchiarelli, Davide et al. “Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.” Cell 162.2 (2015): 412–424.
Version
Author's final manuscript
Abstract
Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here, we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.06.016
