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Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures.


ABSTRACT: 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.

SUBMITTER: Boonekamp KE 

PROVIDER: S-EPMC6642409 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures.

Boonekamp Kim E KE   Kretzschmar Kai K   Wiener Dominique J DJ   Asra Priyanca P   Derakhshan Sepideh S   Puschhof Jens J   López-Iglesias Carmen C   Peters Peter J PJ   Basak Onur O   Clevers Hans H  

Proceedings of the National Academy of Sciences of the United States of America 20190628 29


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 med  ...[more]

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