@article{b59608ac08434a0691d7905021762863,
title = "Stem Cell Lineage Infidelity Drives Wound Repair and Cancer",
abstract = "Tissue stem cells contribute to tissue regeneration and wound repair through cellular programs that can be hijacked by cancer cells. Here, we investigate such a phenomenon in skin, where during homeostasis, stem cells of the epidermis and hair follicle fuel their respective tissues. We find that breakdown of stem cell lineage confinement—granting privileges associated with both fates—is not only hallmark but also functional in cancer development. We show that lineage plasticity is critical in wound repair, where it operates transiently to redirect fates. Investigating mechanism, we discover that irrespective of cellular origin, lineage infidelity occurs in wounding when stress-responsive enhancers become activated and override homeostatic enhancers that govern lineage specificity. In cancer, stress-responsive transcription factor levels rise, causing lineage commanders to reach excess. When lineage and stress factors collaborate, they activate oncogenic enhancers that distinguish cancers from wounds.",
keywords = "cancer, epigenetics, lineage infidelity, regeneration, skin, stem cells, stress response, super-enhancers, transcriptional regulation, wound repair",
author = "Yejing Ge and Gomez, {Nicholas C.} and Adam, {Rene C.} and Maria Nikolova and Hanseul Yang and Akanksha Verma and Lu, {Catherine Pei Ju} and Lisa Polak and Shaopeng Yuan and Olivier Elemento and Elaine Fuchs",
note = "Funding Information: We thank S. Chai for technical assistance; J. Levorse and M. Sribour for assisting with mice experiments; Z. Shen, S. Luo, M. Laurin, S. Ellis, Y. Miao, S. Naik, S. Larsen, K. Lay, and S. Liu for discussions; J. Vidigal, A Ventura (Memorial Sloan Kettering Cancer Institute), C. Vokac, and K. Chang (Cold Spring Harbor Laboratories) for advice in designing CRISPR guides; Comparative Bioscience Center (AAALAC accredited) for care of mice in accordance with NIH guidelines; Rockefeller (C. Zhao, Director) and Weill Cornell Genomics Resource Center (J. Xiang, Director) for sequencing; Flow Cytometry facility (S. Mazel, Director) for cell sorting. E.F. is an investigator of the Howard Hughes Medical Institute. Y.G. is the recipient of a Robertson Therapeutic Development Fund POC VI FUCHS/GE and a Department of Defense Breast Cancer Postdoctoral Fellowship W81XWH-14-1-0047. R.C.A. is an Anderson Cancer Center Graduate Fellow. H.Y. is a Kwanjeong Educational Foundation Graduate Fellow. The work was supported by grants from the National Institutes of Health (R37-AR27883 and R01-AR31737). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = may,
day = "4",
doi = "10.1016/j.cell.2017.03.042",
language = "English (US)",
volume = "169",
pages = "636--650.e14",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}