Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 29, Pages 14630-14638Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1715272116
Keywords
mammalian epidermis; organoids; adult stem cells; interfollicular epidermis
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Funding
- Swiss National Science Foundation (Sinergia Grant) [CRSII3 160738-1]
- Netherlands Organization for Scientific Research (NWO-ZonMW) [114021012]
- Dutch Cancer Society
- gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research (NWO)
- Human Frontier Science Program Organization [LT771/2015]
- VENI grant (NWO-ZonMW) [016.166.140]
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Mammalian epidermal stem cells maintain homeostasis of the skin epidermis and contribute to its regeneration throughout adult life. While 2D mouse epidermal stem cell cultures have been established decades ago, a long-term, feeder cell- and serum-free culture system recapitulating murine epidermal architecture has not been available. Here we describe an epidermal organoid culture system that allows long-term, genetically stable expansion of adult epidermal stem cells. Our epidermal expansion media combines atypically high calcium concentrations, activation of cAMP, FGF, and R-spondin signaling with inhibition of bone morphogenetic protein (BMP) signaling. Organoids are established robustly from adult mouse skin and expand over at least 6 mo, while maintaining the basal-apical organization of the mouse interfollicular epidermis. The system represents a powerful tool to study epidermal homeostasis and disease in vitro.
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