093 Towards modeling ethnic variations in sebaceous lipid production using human iPSC derived sebocytes

Abstract

The sebaceous gland is an essential component of the skin: it is composed of sebocytes which secrete sebum out to the skin surface and maintain its normal lubrication. While different models of human sebocytes have been developped over the past decades, they suffer from restrictions, such as limited yield for primary cultures, or abnormal karyotype for immortalized cell lines. On the other hand, human induced pluripotent stem cells (hiPSC) proliferate indefinitely yet retain their ability to differentiate into any cell type. We achieved large scale production of hiPSC derived sebocytes (PCi-SEB) that display many characteristics of native sebocytes including morphology, marker expression and key functions, while maintaining a normal karyotype. Differentiation of PCi-SEB from Caucasian, Asian and African hiPSC lines allowed us to model in vitro differences in lipid production observed between these ethnic groups. PCi-SEB were differentiated from hiPSC cell lines PCi-CAU, PCi-ASI and PCi-AFR following a proprietary protocol. After thawing, PCi-SEB were cultured on fibronectine in sebocyte culture medium (PhenoCULT-SEB). PCi-SEB displayed an epithelial morphology with prominent lipid droplets in the cytoplasm. KRT7 and MUC1 were expressed in 80-90% of the cells, while functional markers such as PPARG, FADS2, SCD and MC5R were also strongly expressed. On the functional levels, PCi-SEB responded by increased lipid production to linoleic acid, arachidonic acid and testosterone stimulation. They had a high d6/d9 ratio and displayed a normal karyotype. Interestingly, PCi-SEB of Caucasian and Asian origin did not significantly differ in lipid production in their basal state, while PCi-SEB of African origin produced 3-4 folds more lipids. Sebocytes differentiated from hiPSC may represent an attractive in vitro tool to model ethnic variations in sebaceous lipid for the development of personalized drugs or skin cares. Further work is required to increase the repertoire of hiPSC lines.