TY - JOUR
T1 - Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures
AU - Boonekamp, Kim E
AU - Kretzschmar, Kai
AU - Wiener, Dominique J
AU - Asra, Priyanca
AU - Derakhshan, Sepideh
AU - Puschhof, Jens
AU - López-Iglesias, Carmen
AU - Peters, Peter J
AU - Basak, Onur
AU - Clevers, Hans
PY - 2019/7/16
Y1 - 2019/7/16
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.1715272116
DO - 10.1073/pnas.1715272116
M3 - Article
C2 - 31253707
SN - 0027-8424
VL - 116
SP - 14630
EP - 14638
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 29
ER -