Function-driven geometry directs human pilosebaceous unit development
- 1Wellcome Sanger Institute
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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BibTeX
@misc{farr2026functiondriven,
title = {{Function-driven geometry directs human pilosebaceous unit development}},
author = {E. Farr and E. Kritikaki and M. Chroscik and C. Admane and E. Graves and C. Tudor and H. M. Chan and J. Boccacino and J. McWilliam and F. Torabi and K. Chakala and D. Basurto-Lozada and T. Li and A. Binkevich and A. Predeus and M. Prete and M. Panamarova and D. Adao and K. Evans and K. Stewart and L. Steele and E. Winheim and N. H. Gopee and E. Stephenson and M. Patel and C. Hale and L. Gambardella and B. Harpur and C. Smith and D. Horsfall and V. Shanmugiah and L. Parts and D. J. Adams and M. Kasper and A. Dugourd and J. Saez-Rodriguez and A. R. Foster and M. Haniffa},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.745265},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.745265v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Function-driven geometry directs human pilosebaceous unit development
AU - E. Farr
AU - E. Kritikaki
AU - M. Chroscik
AU - C. Admane
AU - E. Graves
AU - C. Tudor
AU - H. M. Chan
AU - J. Boccacino
AU - J. McWilliam
AU - F. Torabi
AU - K. Chakala
AU - D. Basurto-Lozada
AU - T. Li
AU - A. Binkevich
AU - A. Predeus
AU - M. Prete
AU - M. Panamarova
AU - D. Adao
AU - K. Evans
AU - K. Stewart
AU - L. Steele
AU - E. Winheim
AU - N. H. Gopee
AU - E. Stephenson
AU - M. Patel
AU - C. Hale
AU - L. Gambardella
AU - B. Harpur
AU - C. Smith
AU - D. Horsfall
AU - V. Shanmugiah
AU - L. Parts
AU - D. J. Adams
AU - M. Kasper
AU - A. Dugourd
AU - J. Saez-Rodriguez
AU - A. R. Foster
AU - M. Haniffa
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.745265
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.745265v1
AB - 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.
ER -