Function-driven geometry directs human pilosebaceous unit development

Elias Farr; Efpraxia Kritikaki; Marta A. Chroscik; Chloe Admane; Emily J Graves; Catherine L. Tudor; Hon Man Chan; Jacqueline Marcia Boccacino; Joseph McWilliam; Fereshteh Torabi; Keerthi Priya Chakala; Daniela Basurto-Lozada; Tong Li; Aljes Binkevich; Alexander V. Predeus; Martin Prete; Maryna Panamarova; Diana Adão; Kim Evans; Kris Stewart; Lloyd Steele; Elena Winheim; Nusayhah Hudaa Gopee; Emily Stephenson; Minal J Patel; Claire Anne Hale; Laure Gambardella; Xinyi Du-Harpur; Catherine H. Smith; Dave Horsfall

doi:10.64898/2026.08.31.745265

Developmental BiologybioRxivSep 4, 2026

Preprint

Function-driven geometry directs human pilosebaceous unit development

Elias Farr iD, Efpraxia Kritikaki iD, Marta A. Chroscik iD, Chloe Admane iD, Emily J Graves iD, Catherine L. Tudor iD, Hon Man Chan, Jacqueline Marcia Boccacino iD, Joseph McWilliam iD, Fereshteh Torabi iD, Keerthi Priya Chakala iD, Daniela Basurto-Lozada iD, Tong Li iD, Aljes Binkevich iD, Alexander V. Predeus iD, Martin Prete iD, Maryna Panamarova iD, Diana Adão iD, Kim Evans, Kris Stewart, Lloyd Steele iD, Elena Winheim iD, Nusayhah Hudaa Gopee iD, Emily Stephenson iD, Minal J Patel, , Muzlifah A. Haniffa iD

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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