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Long-Term In Vitro Expansion of Epithelial Stem Cells Enabled by Pharmacological Inhibition of PAK1-ROCK-Myosin II and TGF-β Signaling.

Cell reports | 2018

Despite substantial self-renewal capability in vivo, epithelial stem and progenitor cells located in various tissues expand for a few passages in vitro in feeder-free condition before they succumb to growth arrest. Here, we describe the EpiX method, which utilizes small molecules that inhibit PAK1-ROCK-Myosin II and TGF-β signaling to achieve over one trillion-fold expansion of human epithelial stem and progenitor cells from skin, airway, mammary, and prostate glands in the absence of feeder cells. Transcriptomic and epigenomic studies show that this condition helps epithelial cells to overcome stresses for continuous proliferation. EpiX-expanded basal epithelial cells differentiate into mature epithelial cells consistent with their tissue origins. Whole-genome sequencing reveals that the cells retain remarkable genome integrity after extensive in vitro expansion without acquiring tumorigenicity. EpiX technology provides a solution to exploit the potential of tissue-resident epithelial stem and progenitor cells for regenerative medicine.

Pubmed ID: 30332641 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG009391
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG007175
  • Agency: NCI NIH HHS, United States
    Id: U01 CA200060
  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES024992
  • Agency: NIDA NIH HHS, United States
    Id: R25 DA027995
  • Agency: NIEHS NIH HHS, United States
    Id: U24 ES026699
  • Agency: NHLBI NIH HHS, United States
    Id: R43 HL144177
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG007354

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