PT  - JOURNAL ARTICLE
AU  - Tatsuto Kageyama
AU  - Akihiro Shimizu
AU  - Riki Anakama
AU  - Rikuma Nakajima
AU  - Kohei Suzuki
AU  - Yusuke Okubo
AU  - Junji Fukuda
TI  - Reprogramming of three-dimensional microenvironments for <em>in vitro</em> hair follicle induction
AID  - 10.1101/2022.06.13.495917
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.13.495917
4099  - http://biorxiv.org/content/early/2022/06/16/2022.06.13.495917.short
4100  - http://biorxiv.org/content/early/2022/06/16/2022.06.13.495917.full
AB  - During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached ∼3 mm in culture. Typical trichogenic signaling pathways were upregulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, production and transportation of melanosomes were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, for evaluating hair growth as well as the inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment.Teaser In tissue morphogenesis, different types of cells harmonize in a pre-programmed manner using messenger systems such as epithelial-mesenchymal interactions. Organoids are a promising tool to elucidate such mechanisms on a molecular level. This work describes a strategy for reprograming three-dimensional microenvironments to trigger the initiation of in vitro regeneration of hair follicle organoids. Hair follicle organoids generated fully matured hair follicles, enabling the monitoring of hair follicle morphogenesis in vitro and determination of signaling pathways involved in early hair follicle morphogenesis. The principles uncovered herein may be relevant to other organ systems and will contribute to our understanding of developmental phenomena in physiological and pathological processes, eventually opening up new research avenues for the development of new treatment strategies.Competing Interest StatementThe authors have declared no competing interest.