The hair follicle is a mini-organ that is regenerated from stem cells in the adult. Significant progress has been made in defining and studying the stem cells of the follicular epithelium that regenerate the follicle. However their activation and the differentiation of their progeny to regenerate hair follicles is guided by a specialized mesenchymal population, the dermal papilla (DP). While the importance of these DP cells in follicle formation is clearly established, the nature of the signals generated by them and the ways in which they may change to guide keratinocytes through the successive tasks required to rebuild a follicle and elaborate a hair shaft remain poorly understood. This is in part because the techniques to purify DP cells and manipulate gene expression in them have lagged behind those used to study the epithelial components of the follicle. We have developed novel approaches that allow the purification in bulk of both DP cells and their immediate precursors in development. We have also developed assays to evaluate the inductive activity of these cells during follicle neogenesis. Finally we have developed methods to manipulate gene expression specifically in dermal papilla cells in the context of intact follicles. We will employ these novel reagents and techniques to identify the changes in gene expression that characterize the dermal papilla at different stages in follicle formation, regeneration, and degeneration. The function of these genes in follicle formation and cycling will be tested both in vivo and in vitro. The results of this work will have direct implications for the management of hair growth, regeneration and loss, and also for the management of severe skin wounds where the ability to regenerate cutaneous appendages remains an elusive goal. They will also have broader impact in the fields of stem cell biology and tissue engineering, not only because the hair follicle serves as an important model system in these fields, but because DP are a source of SKPs, an adult derived progenitor population that holds therapeutic promise.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR055256-05
Application #
8117609
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Baker, Carl
Project Start
2007-08-05
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$350,436
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Chi, Woo; Morgan, Odysseas; Wu, Eleanor et al. (2017) Stabilization of ?-Catenin Does Not Increase Dermal Papilla Cell Number in the Hair Follicle. J Invest Dermatol 137:245-246
Kashiwagi, Mariko; Hosoi, Junichi; Lai, Jen-Feng et al. (2017) Direct control of regulatory T cells by keratinocytes. Nat Immunol 18:334-343
Kamberov, Yana G; Karlsson, Elinor K; Kamberova, Gerda L et al. (2015) A genetic basis of variation in eccrine sweat gland and hair follicle density. Proc Natl Acad Sci U S A 112:9932-7
Rieder, Sadiye Amcaoglu; Metidji, Amina; Glass, Deborah Dacek et al. (2015) Eos Is Redundant for Regulatory T Cell Function but Plays an Important Role in IL-2 and Th17 Production by CD4+ Conventional T Cells. J Immunol 195:553-63
Chi, Woo; Wu, Eleanor; Morgan, Bruce A (2015) Earlier-born secondary hair follicles exhibit phenotypic plasticity. Exp Dermatol 24:265-8
Morgan, Bruce A (2014) The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harb Perspect Med 4:a015180
Kamberov, Yana G; Wang, Sijia; Tan, Jingze et al. (2013) Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152:691-702
Yoshida, Toshimi; Landhuis, Esther; Dose, Marei et al. (2013) Transcriptional regulation of the Ikzf1 locus. Blood 122:3149-59
Chi, Woo; Wu, Eleanor; Morgan, Bruce A (2013) Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline. Development 140:1676-83
Morgan, Bruce A (2011) Developmental biology: a hair-raising tale. Nature 471:586-7

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