Stem Cell Lineage Infidelity Drives Wound Repair and Cancer.

TitleStem Cell Lineage Infidelity Drives Wound Repair and Cancer.
Publication TypeJournal Article
Year of Publication2017
AuthorsGe Y, Gomez NC, Adam RC, Nikolova M, Yang H, Verma A, Lu CPei-Ju, Polak L, Yuan S, Elemento O, Fuchs E
Date Published2017 05 04
KeywordsAnimals, Carcinoma, Squamous Cell, Cell Line, Tumor, Cell Lineage, Chromatin, Epidermal Cells, Epidermis, Hair Follicle, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Skin, Skin Neoplasms, Stem Cells, Transcription Factors, Transcriptome, Transplantation, Heterologous, Wound Healing

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.

Alternate JournalCell
PubMed ID28434617
PubMed Central IDPMC5510746
Grant ListR01 AR027883 / AR / NIAMS NIH HHS / United States
R01 AR031737 / AR / NIAMS NIH HHS / United States
R01 AR050452 / AR / NIAMS NIH HHS / United States
R37 AR027883 / AR / NIAMS NIH HHS / United States