The spatial relationship between stem cells and their progeny in the basallayer of human epidermis: a new view based on whole-mount labelling and lineage analysis
Ub. Jensen et al., The spatial relationship between stem cells and their progeny in the basallayer of human epidermis: a new view based on whole-mount labelling and lineage analysis, DEVELOPMENT, 126(11), 1999, pp. 2409-2418
In order to examine the spatial organisation of stem cells and their progen
y in human epidermis, we developed a method for whole-mount epidermal immun
ofluorescence labelling using high surface beta 1 integrin expression as a
stem cell marker. We confirmed that there are clusters of high beta 1 integ
rin-expressing cells at the tips of the dermal papillae in epidermis from s
everal body sites, whereas alpha 6 integrin expression is more uniform. The
majority of actively cycling cells detected by Ki67 or bromodeoxyuridine l
abelling were found in the beta 1 integrin-dull, transit amplifying populat
ion and integrin-negative, keratin 10-positive cells left the basal layer e
xclusively from this compartment. When we examined p53-positive clones in s
un-exposed epidermis, we found two types of clone that differed in size and
position in a way that was consistent with the founder cell being a stem o
r transit amplifying cell. The patterning of the basal layer implies that t
ransit amplifying cells migrate over the basement membrane away from the st
em cell clusters. In support of this, isolated beta 1 integrin-dull keratin
ocytes were more motile on type IV collagen than beta 1 integrin-bright ker
atinocytes and EGFP-labelled stem cell clones in confluent cultured sheets
were compact, whereas transit amplifying clones were dispersed. The combina
tion of whole-mount labelling and lineage marking thus reveals features of
epidermal organisation that were previously unrecognised.