Role of adipocytes in human hair follicle cycling
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
The aim of this ICASE PhD project is to investigate the role of adipose tissue in hair follicle growth and cycling as a basis for novel therapeutic interventions. The research is in partnership with Unilever R&D.
Adipose tissue is a key constituent of human skin whose functions extend far beyond energy storage and thermoregulation. Several mutant mouse models with defects in adipocytes have elucidated some of these previously unknown roles. For example, a genetic mouse model lacking early B-cell factor 1(Ebf1) exhibited reduced intradermal adipocytes. Hair follicles in these mice failed to re-enter the anagen phase of the hair growth cycle and remained in the resting telogen stage (Hesslein 2009). This demonstrates the importance of pre-adipocytes in the promotion of telogen to anagen transition during the hair follicle cycle in mice, and has raised increasing interest in the role of the adipocyte-hair follicle communication in the regulation of hair growth.
However, the adipocyte-hair follicle communication in human skin, and how it may be manipulated in a clinically or cosmetically desirable manner, is entirely unknown. There is increasing insight into the importance of this bidirectional communication for hair follicle cycling and (murine) wave pattern formation, as well as adipocyte differentiation and function (Plikus 2008, Schmidt 2012, Donati 2014). As such, improved characterisation of this communication could provide novel targets and strategies for therapeutic intervention.
The mechanism behind the potential interaction of adipocyte signals with the hair follicle is not well understood but platelet derived growth factor (PDGF) signalling may play a significant role. PDGFA mRNA is significantly elevated in adipocyte precursor cells (Festa 2011) and mice lacking PDGFA show a delay in hair follicle stem cell activation (Tomita 2006). There is strong possibility that understanding and influencing signalling of intradermal adipocytes in the hair follicle microenvironment could impact the hair follicle with potential benefits such as promoting hair growth & prolonging the follicle growing phase.
This study will span the Centre for Dermatology Research and Unilever R&D facility, Colworth. Extensive training will be provided in histology, immunohistochemistry and state-of-the-art double-immunostaining and image analysis techniques. Carina will also become familiar with light, fluorescent and confocal microscopy, qRT-PCR and gene silencing in intact human skin/hair follicles.
Adipose tissue is a key constituent of human skin whose functions extend far beyond energy storage and thermoregulation. Several mutant mouse models with defects in adipocytes have elucidated some of these previously unknown roles. For example, a genetic mouse model lacking early B-cell factor 1(Ebf1) exhibited reduced intradermal adipocytes. Hair follicles in these mice failed to re-enter the anagen phase of the hair growth cycle and remained in the resting telogen stage (Hesslein 2009). This demonstrates the importance of pre-adipocytes in the promotion of telogen to anagen transition during the hair follicle cycle in mice, and has raised increasing interest in the role of the adipocyte-hair follicle communication in the regulation of hair growth.
However, the adipocyte-hair follicle communication in human skin, and how it may be manipulated in a clinically or cosmetically desirable manner, is entirely unknown. There is increasing insight into the importance of this bidirectional communication for hair follicle cycling and (murine) wave pattern formation, as well as adipocyte differentiation and function (Plikus 2008, Schmidt 2012, Donati 2014). As such, improved characterisation of this communication could provide novel targets and strategies for therapeutic intervention.
The mechanism behind the potential interaction of adipocyte signals with the hair follicle is not well understood but platelet derived growth factor (PDGF) signalling may play a significant role. PDGFA mRNA is significantly elevated in adipocyte precursor cells (Festa 2011) and mice lacking PDGFA show a delay in hair follicle stem cell activation (Tomita 2006). There is strong possibility that understanding and influencing signalling of intradermal adipocytes in the hair follicle microenvironment could impact the hair follicle with potential benefits such as promoting hair growth & prolonging the follicle growing phase.
This study will span the Centre for Dermatology Research and Unilever R&D facility, Colworth. Extensive training will be provided in histology, immunohistochemistry and state-of-the-art double-immunostaining and image analysis techniques. Carina will also become familiar with light, fluorescent and confocal microscopy, qRT-PCR and gene silencing in intact human skin/hair follicles.
Publications
Nicu C
(2018)
A guide to studying human dermal adipocytes in situ.
in Experimental dermatology
Nicu C
(2019)
Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy and lipolysis during catagen in the human hair cycle?
in Experimental dermatology
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/N503605/1 | 01/10/2015 | 30/09/2019 | |||
| 1640601 | Studentship | BB/N503605/1 | 01/10/2015 | 30/09/2019 | Carina Nicu |
| Description | Our 2018 methods review (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13549) offers an introduction into studying human fat cells and the tools that can be utilized for these aims. In addition, it summarizes a few novel findings regarding what proteins fat cells in scalp skin express. In our 2019 publication, we hypothesized that fat cells around dying hair follicles in human scalp appear to be shrinking in size compared to fat cells around growing hair follicles, and releasing cholesterol as a by-product (https://onlinelibrary.wiley.com/doi/abs/10.1111/exd.13904). These preliminary findings may pave the way to identifying what effect cholesterol from local fat cells may have upon human hair follicle growth. In addition, this may lead to research focusing on whether hair follicles themselves play a role in increasing or decreasing dermal fat size. |
| Exploitation Route | Our methods review can be used by a multitude of researchers with the purpose of beginning to study dermal fat cells using different techniques. The hypothesis letter that we published may be used to further explore the interesting observations on the changes in ultrastructure within human dermal fat cells between anagen and catagen HFs, and the effect of cholesterol released by fat cells upon hair cycle progression. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | My doctoral project has more fully characterise human dermal adipose tissue. In addition the project will identify some of the key biological factors secreted by human dermal adipocytes and to understand how these impact the physiology and cycling of the human hair follicle. In doing so, this this could lead to new intervention strategies to aid patients with disorders of the hair follicle such as alopecia as well as cosmetic hair conditions via the projects collaborative industrial partner. |
| First Year Of Impact | 2017 |
| Sector | Manufacturing, including Industrial Biotechology |
| Impact Types | Societal |