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Function-driven geometry directs human pilosebaceous unit development

Farr, E.; Kritikaki, E.; Chroscik, M.; Admane, C.; Graves, E.; Tudor, C.; Chan, H. M.; Boccacino, J.; McWilliam, J.; Torabi, F.; Chakala, K.; Basurto-Lozada, D.; Li, T.; Binkevich, A.; Predeus, A.; Prete, M.; Panamarova, M.; Adao, D.; Evans, K.; Stewart, K.; Steele, L.; Winheim, E.; Gopee, N. H.; Stephenson, E.; Patel, M.; Hale, C.; Gambardella, L.; Harpur, B.; Smith, C.; Horsfall, D.; Shanmugiah, V.; Parts, L.; Adams, D. J.; Kasper, M.; Dugourd, A.; Saez-Rodriguez, J.; Foster, A. R.; Haniffa, M.

2026-09-01 developmental biology
10.64898/2026.08.31.745265 bioRxiv
Show abstract

Single-cell technologies have generated cell censuses of tissues, however, how tissue geometry reflects functional needs remains poorly characterized. The human pilosebaceous unit offers a tractable model, a prenatally-formed complex mini-organ combining hair and sebum production with a stem cell reservoir. Using histomorphology, spatial transcriptomics, and single-cell multiomics on the same human prenatal scalp skin samples (8-19 post-conception weeks), integrated and analyzed using machine learning approaches, we built a spatiotemporal map of pilosebaceous unit development. We demonstrate that epithelial-mesenchymal interactions coordinate cellular fate and organogenesis, using an in vitro hair-bearing skin organoid model to validate this tissue-patterning. In addition, we show sebaceous gland developmental programmes are overcome during tumor formation. Our large-scale multi-modal analysis provides a unique framework for understanding form and function of tissues with applications in tissue engineering and pathology.

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