Analysis of stem cell fate decisions in epidermis by in vivo lineage marking

Lead Research Organisation: Queen Mary, University of London
Department Name: Blizard Institute of Cell and Molecular

Abstract

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Technical Summary

The best-characterized stem cell compartment in mouse epidermis is in the hair follicle bulge. DNA label-retaining cells (LRC) cluster in this region, where expression of the previously reported stem cell markers CD34 and keratin 15 also is high. It has been suggested that LRC likely only represent a subset of the stem cells that are present in the epidermis. In this study, I propose using permanent, in vivo lineage marking to assess the potential of epidermal stem cells in normal skin, under circumstances where epidermal development is disturbed due to aberrant expression of members of the Wnt/ -catenin pathway, and during tumour formation. In addition, I will characterize the nature of a population of hair follicle keratinocytes that are identified by the cell surface marker MTS24. These keratinocytes give rise to large colonies with great efficiency when cultured at low density in vitro. MTS24-positive cells will be characterized with respect to their self-renewal capacity, ability to differentiate into different lineages both in vitro and in vivo, and global gene expression pattern. MTS24-positive cells are localized in an uncharacterized region of the hair follicle between the bulge and the sebaceous glands. Keratinocytes located in this region tend not to be label retaining and lack expression of CD34 and keratin 15. To compare the lineage potential of keratinocytes derived from the MTS24-positive region of the hair follicle to those derived from the bulge, transgenic mice will be generated which target an activatable form of Cre to each of these two regions. Taken together, the studies described in this proposal will demonstrate the utility of in vivo differential somatic cell marking to address key questions in epidermal biology. This approach will be used to characterize whether a new population of keratinocytes represent a new reservoir of epidermal stem cells or a population of lineage-restricted progenitor cells.
 
Description Barts and The London Charitable Trust, Project Grant
Amount £96,358 (GBP)
Organisation Barts Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2007 
End 07/2009
 
Description British Skin Foundation
Amount £78,000 (GBP)
Organisation British Skin Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2011 
End 08/2013
 
Title MTS24 Microarray 
Description Results from Microarray Screen 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact This data will be published in a peer-reviewed journal. Therefore, it will serve as a foundation for future projects in my laboratory and will be available to other scientists. 
 
Description Characterisation of MTS24 positive keratinocytes 
Organisation Monash University
Country Australia 
Sector Academic/University 
PI Contribution We have used the MTS24 antibody to characterise a novel population of follicular keratinocytes
Collaborator Contribution Use of a proprietary antibody
Impact Pubmed ID: 16818453
 
Description Centre of the Cell Ambassador 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Approximately 20-30 students per session visit Barts and the London's 'Centre of the Celll'. I tell them a bit about my research and field questions about life as a scientist before and after the session. During the session I circulate to interact with individual students as they learn from the interactive activities.

N/A
Year(s) Of Engagement Activity 2010,2011
 
Description School Visits - London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Barts and The London Centre of the Cell runs a Meet the Scientist Seminar program in which we present our research to local secondary students/teachers. I have presented two lectures on campus and lectures at local schools (Southgate and Hackney).

Outstanding interactions with local students. I have received invitations to return to several of the schools that I visited.
Year(s) Of Engagement Activity 2009,2010,2011