CD133 defines hair-inductive cells in the dermal papilla

Abstract A major contributing factor to the failure of cell-based human hair follicle (HF) engineering is our inability to cultivate highly specialized, inductive mesenchymal fibroblasts, which reside in a unique niche at the HF base, called the dermal papilla (DP). We and other groups have discover...

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Main Authors: Huangying Zhao, Linli Zhou, Lindsey G. Siegfried, Steven Boyce, Dorothy Supp, Thomas Andl, Yuhang Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05487-y
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author Huangying Zhao
Linli Zhou
Lindsey G. Siegfried
Steven Boyce
Dorothy Supp
Thomas Andl
Yuhang Zhang
author_facet Huangying Zhao
Linli Zhou
Lindsey G. Siegfried
Steven Boyce
Dorothy Supp
Thomas Andl
Yuhang Zhang
author_sort Huangying Zhao
collection DOAJ
description Abstract A major contributing factor to the failure of cell-based human hair follicle (HF) engineering is our inability to cultivate highly specialized, inductive mesenchymal fibroblasts, which reside in a unique niche at the HF base, called the dermal papilla (DP). We and other groups have discovered a unique DP fibroblast subpopulation that can be identified by the cell surface marker CD133. However, the biological difference between CD133-positive (CD133+) and CD133-negative (CD133-) DP cells remains unknown. Using a newly developed double fluorescent transgenic mouse strain, we isolated CD133 + and CD133- DP cells from mouse anagen HFs. In monolayer culture, both DP populations gradually lost expression of the anagen DP signature gene, versican. When maintained in three-dimensional spheroid culture, versican expression was restored in both CD133 + and CD133- DP cells. Importantly, CD133 + DP spheroids appeared more compact, showed stronger alkaline phosphatase staining (AP), and expressed higher levels of DP signature genes. In in vivo skin reconstitution assays, mice grafted with CD133 + DP spheroids grew more hairs in healed wounds than those grafted with CD133- DP spheroids. The data underscore the importance of CD133 + DP cells as a driver of HF formation, which may present a unique opportunity to improve the use of human DP cells in tissue-engineered skin substitutes (TESS).
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spelling doaj-art-2a151cf9084f4de7b94f16f450bb84542025-08-20T03:37:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-05487-yCD133 defines hair-inductive cells in the dermal papillaHuangying Zhao0Linli Zhou1Lindsey G. Siegfried2Steven Boyce3Dorothy Supp4Thomas Andl5Yuhang Zhang6Division of Pharmaceutical Science, College of Pharmacy, University of CincinnatiDivision of Pharmaceutical Science, College of Pharmacy, University of CincinnatiDivision of Pharmaceutical Science, College of Pharmacy, University of CincinnatiDepartment of Surgery, University of Cincinnati College of MedicineDepartment of Surgery, University of Cincinnati College of MedicineBurnett School of Biological Sciences, University of Central FloridaDivision of Pharmaceutical Science, College of Pharmacy, University of CincinnatiAbstract A major contributing factor to the failure of cell-based human hair follicle (HF) engineering is our inability to cultivate highly specialized, inductive mesenchymal fibroblasts, which reside in a unique niche at the HF base, called the dermal papilla (DP). We and other groups have discovered a unique DP fibroblast subpopulation that can be identified by the cell surface marker CD133. However, the biological difference between CD133-positive (CD133+) and CD133-negative (CD133-) DP cells remains unknown. Using a newly developed double fluorescent transgenic mouse strain, we isolated CD133 + and CD133- DP cells from mouse anagen HFs. In monolayer culture, both DP populations gradually lost expression of the anagen DP signature gene, versican. When maintained in three-dimensional spheroid culture, versican expression was restored in both CD133 + and CD133- DP cells. Importantly, CD133 + DP spheroids appeared more compact, showed stronger alkaline phosphatase staining (AP), and expressed higher levels of DP signature genes. In in vivo skin reconstitution assays, mice grafted with CD133 + DP spheroids grew more hairs in healed wounds than those grafted with CD133- DP spheroids. The data underscore the importance of CD133 + DP cells as a driver of HF formation, which may present a unique opportunity to improve the use of human DP cells in tissue-engineered skin substitutes (TESS).https://doi.org/10.1038/s41598-025-05487-yHair follicleTissue engineeringKeratinocytesFibroblasts
spellingShingle Huangying Zhao
Linli Zhou
Lindsey G. Siegfried
Steven Boyce
Dorothy Supp
Thomas Andl
Yuhang Zhang
CD133 defines hair-inductive cells in the dermal papilla
Scientific Reports
Hair follicle
Tissue engineering
Keratinocytes
Fibroblasts
title CD133 defines hair-inductive cells in the dermal papilla
title_full CD133 defines hair-inductive cells in the dermal papilla
title_fullStr CD133 defines hair-inductive cells in the dermal papilla
title_full_unstemmed CD133 defines hair-inductive cells in the dermal papilla
title_short CD133 defines hair-inductive cells in the dermal papilla
title_sort cd133 defines hair inductive cells in the dermal papilla
topic Hair follicle
Tissue engineering
Keratinocytes
Fibroblasts
url https://doi.org/10.1038/s41598-025-05487-y
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