@article{f4b2b30669254073b0b3037afff87c11,
title = "Asymmetric Cell Division of Fibroblasts is An Early Deterministic Step to Generate Elite Cells during Cell Reprogramming",
abstract = "Cell reprogramming is considered a stochastic process, and it is not clear which cells are prone to be reprogrammed and whether a deterministic step exists. Here, asymmetric cell division (ACD) at the early stage of induced neuronal (iN) reprogramming is shown to play a deterministic role in generating elite cells for reprogramming. Within one day, fibroblasts underwent ACD, with one daughter cell being converted into an iN precursor and the other one remaining as a fibroblast. Inhibition of ACD significantly inhibited iN conversion. Moreover, the daughter cells showed asymmetric DNA segregation and histone marks during cytokinesis, and the cells inheriting newly replicated DNA strands during ACD became iN precursors. These results unravel a deterministic step at the early phase of cell reprogramming and demonstrate a novel role of ACD in cell phenotype change. This work also supports a novel hypothesis that daughter cells with newly replicated DNA strands are elite cells for reprogramming, which remains to be tested in various reprogramming processes.",
keywords = "asymmetric cell division, cell fate determination, direct reprogramming, epigenetic state",
author = "Yang Song and Jennifer Soto and Pingping Wang and Qin An and Xuexiang Zhang and Hong, {Soon Gweon} and Lee, {Luke P.} and Guoping Fan and Li Yang and Song Li",
note = "Funding Information: The authors thank Dr. Marius Wernig at Stanford University for providing the constructs of BAM for reprogramming experiments. The authors also thank Dr. Siavash K. Kurdistani at the University of California, Los Angeles for insightful discussion. The single‐cell RNA sequencing was performed at the Technology Center for Genomics and Bioinformatics at UCLA. The authors were supported in part by a UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Innovation Award, a grant from the National Institute of Health (HL121450, to S.L.), a postdoctoral fellowship from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under the Ruth L. Kirschstein National Research Service Award (T32AR059033, to J.S.), and a grant from National Nature Science Foundation of China (11532004, to L.Y.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",
year = "2021",
month = apr,
day = "7",
doi = "10.1002/advs.202003516",
language = "English",
volume = "8",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "7",
}