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Abstract
In spite of its clinical importance, little is known about the stem-cell compartment
of the human oesophageal epithelium [1,2]. The epithelial basal layer consists of
two distinct zones, one overlying the papillae of the supporting connective tissue
(PBL) and the other covering the interpapillary zone (IBL) [3]. In examining the oesophageal
basal layer, we found that proliferating cells were rare in the IBL and a high proportion
of mitoses were asymmetrical, giving rise to one basal daughter and one suprabasal,
differentiating daughter. In the PBL, mitoses were more frequent and predominantly
symmetrical. The IBL was characterised by low expression of ?1 integrins and high
expression of the beta2 laminin chain. By combining fluorescence-activated cell sorting
(FACS) with in vitro clonal analysis, we obtained evidence that the IBL is enriched
for stem cells. A normal oesophageal epithelium with asymmetric divisions was reconstituted
on denuded oesophageal connective tissue. In contrast, asymmetric divisions were not
sustained on skin connective tissue, and the epithelium formed resembled epidermis.
We propose that stem cells located in the IBL give rise to differentiating daughters
through asymmetric divisions in response to cues from the underlying basement membrane.
Until now, stem-cell fate in stratified squamous epithelia was believed to be achieved
largely through populational asymmetry [4-6].