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Title: Stem cell fate in cultured human epidermis
Author: Rytina, Edward Robert Charles
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1997
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The proliferating cells in the epidermis, stem cells and transit amplifying cells, can be separated to form enriched populations of each type by their ability to adhere to extra cellular matrix. Stem cells adhere rapidly to type IV collagen and give rise to large colonies in culture whereas slowly adhering transit amplifying cells form small colonies of terminally differentiated cells only. I have developed and used a variety of lineage markers to follow individual cells and their progeny and study how different populations of cultured cells behave when at confluence, mimicking the epidermis in a steady state when the rate of cell renewal is balanced by that of differentiation. Using various culture techniques I have looked at how the proliferating and differentiating cells of the epidermis may be organised in vivo and whether there is a relationship between the extracellular matrix of the dermis and the behaviour of the different types of epidermal cells in the steady state. I have evidence from lineage analysis that clones derived from the putative stem cell population are large and long lived compared to clones founded by the transit amplifying population which are rapidly lost from reconstituted epidermis. I have also shown that the keratinocytes which contribute clones to a confluent cultured sheet, the stem cells, are likely to be a heterogenous population with variable fates. By investigating the expression of adhesion molecules in the epidermis and of extracellular matrix in the basement membrane it is possible to suggest a model for the control of cell fate and stem cell longevity. I have evidence that variability of ?1 integrin expression in basal keratinocytes is accompanied by differences in cadherin expression and that the level of collagen IV varies in the basement membrane, potentially contributing to the definition of the stem cell niche.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available