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Stem Cell Lineage Infidelity Drives Wound Repair and Cancer.

Cell | 2017

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.

Pubmed ID: 28434617 RIS Download

Associated grants

  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR027883
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR031737
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR050452
  • Agency: NIAMS NIH HHS, United States
    Id: R37 AR027883

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This is a list of tools and resources that we have found mentioned in this publication.


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