@article{de06e1b489f847ca877182c454dc43f5,
title = "Dynamic single-cell imaging of direct reprogramming reveals an early specifying event",
abstract = "The study of induced pluripotency often relies on experimental approaches that average measurements across a large population of cells, the majority of which do not become pluripotent. Here we used high-resolution, time-lapse imaging to trace the reprogramming process over 2 weeks from single mouse embryonic fibroblasts (MEFs) to pluripotency factor-positive colonies. This enabled us to calculate a normalized cell-of-origin reprogramming efficiency that takes into account only the initial MEFs that respond to form reprogrammed colonies rather than the larger number of final colonies. Furthermore, this retrospective analysis revealed that successfully reprogramming cells undergo a rapid shift in their proliferative rate that coincides with a reduction in cellular area. This event occurs as early as the first cell division and with similar kinetics in all cells that form induced pluripotent stem (iPS) cell colonies. These data contribute to the theoretical modeling of reprogramming and suggest that certain parts of the reprogramming process follow defined rather than stochastic steps.",
author = "Smith, {Zachary D.} and Iftach Nachman and Aviv Regev and Alexander Meissner",
note = "Funding Information: We thank A. Carpenter and M. Bray from the Broad Imaging Platform for help with the initial CellProfiler image analysis pipeline. We thank E.S. Lander and C. Bock and R.P. Koche for critical reading of the manuscript as well as M. Thomson, M. Staller, A. De Los Angeles and J. Dennett for technical assistance and intellectual input. I.N. was supported by a Merck postdoctoral fellowship and an Alon fellowship. A.R. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, an National Institutes of Health Pioneer Award and the Sloan Foundation. A.R. is an Early Career Scientist of the Howard Hughes Medical Institute and an Investigator of the Merkin Foundation for Stem Cell Research at the Broad Institute. A.M. was supported by the Pew Charitable Trust and a New Investigator grant by the Massachusetts Life Science Center (MLSC). This work was funded by the Pew and MLSC.",
year = "2010",
month = may,
doi = "10.1038/nbt.1632",
language = "אנגלית",
volume = "28",
pages = "521--526",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "5",
}