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.

doi:10.64898/2026.08.31.745265

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bioRxiv · 10.64898/2026.08.31.745265

Function-driven geometry directs human pilosebaceous unit development

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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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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. Function-driven geometry directs human pilosebaceous unit development. https://doi.org/10.64898/2026.08.31.745265

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