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Edited by Zena Werb, University of California, San Francisco, CA, and approved September 5, 2013 (received for review May 28, 2013)
Significance
Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
Abstract
De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin.
Footnotes
- ↵1To whom correspondence may be addressed. E-mail: amc65{at}columbia.edu or colin.jahoda{at}durham.ac.uk.
This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance.
Author contributions: C.A.H., C.A.B.J., and A.M.C. designed research; C.A.H., J.C.C., and J.E.C. performed research; C.A.H., C.A.B.J., and A.M.C. analyzed data; and C.A.H., C.A.B.J., and A.M.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE44765).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1309970110/-/DCSupplemental.
De novo human hair-follicle induction
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