Department of Medicine and Therapeutics, University College Dublin, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
(e-mail: John.Seery{at}ucd.ie )
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Summary |
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Key words: Oesophagus, Epithelium, Stem cell, Barrett's oesophagus, Asymmetric
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The oesophageal epithelium |
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The stem cell model |
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In many invertebrate systems, stem cell division always gives rise to one
stem cell daughter and one transit amplifying cell. Such `invariant asymmetry'
is rare in adult mammalian tissues (Watt
and Hogan, 2000). In most mammalian tissues, stem cell division
has three possible outcomes: the generation of two stem cells, two transit
amplifying cells or one daughter cell of each type. In the steady state, the
balance between stem and transit amplifying cell numbers is maintained in the
tissue as a whole by multiple feedback loops (`populational asymmetry')
(Watt and Hogan, 2000
).
Many issues concerning the nature of epithelial stem cells remain to be
resolved, and there is a growing realization that there may be more plasticity
in adult tissues than the stem/transit-amplifying-cell model predicts
(Morrison et al., 1997;
Vogel, 2000
). However, it
provides a useful framework for us to conceptualize cell behavior in vivo and
also makes several predictions that allow identification and isolation of
putative human stem cells. Firstly, relative to the transit amplifying
population, stem cells should proliferate less frequently in vivo in the
steady state. In addition, as the progeny of transit cells undergo terminal
differentiation after several rounds of division, stem cells have a higher
proliferative capacity both in vivo and in vitro. Secondly, the difference in
function between stem cells and transit amplifying cells is likely to be
reflected in different levels of expression of functionally relevant
molecules. Identification of such molecules could allow the isolation and
separation of the two cell types. Thirdly, because stem cells do not generally
initiate a program of differentiation, they are `phenotypically primitive',
that is, they do not express differentiation markers characteristic of the
tissue.
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Identification and isolation of oesophageal epithelial stem cells |
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Cells in the IBL are thus candidates for oesophageal epithelial stem cells. They proliferate relatively infrequently in vivo, and their division yields one daughter cell that remains in an area of low proliferative activity (a putative stem cell) and one that enters an area of high proliferative activity (a putative transit amplifying cell).
Interpapillary basal layer cells have a high in vitro proliferative
capacity
The level of expression of adhesion molecules is not uniform in the basal
layer of the epidermis (Jones and Watt,
1993; Moles and Watt,
1997
). In the interfollicular epidermis, basal keratinocytes on
the dermal papillae express high levels of ß1 integrin compared with
basal cells in the rete ridges (Jensen et
al., 1999
). Epidermal basal cells can be separated from suprabasal
cells on the basis of their forward- and side-scatter characteristics by
fluorescence activated cell sorting (FACS)
(Jones and Watt, 1993
). Jones
and Watt isolated interfollicular basal epidermal keratinocytes by using this
technique and further separated them on the basis of their relative levels of
ß1 integrin expression. They showed that the 20% of basal cells
expressing the highest level of ß1 integrin are enriched for cells
capable of forming large, rapidly proliferating colonies (>32 cells after
two weeks of culturing) in vitro. They argued that such colonies are likely to
arise from stem cells. Therefore, the `integrin bright' region of the dermal
papillae represents the stem cell compartment of the epidermal basal layer
(Jones and Watt, 1993
;
Jensen et al., 1999
).
Basal cells from the oesophageal epithelium can also be separated from
suprabasal keratinocytes on the basis of their FACS profile
(Jankowski et al., 1992a;
Seery and Watt, 2000
).
In addition, ß1 integrin expression is also predictably heterogeneous
in the oesophageal basal layer. Surprisingly, cells in the IBL express lower
levels of this molecule compared with cells in the PBL. However, when cells
from the two regions are separated by FACS on the basis of ß1 integrin
levels and then grown at clonal density, IBL cells are consistently two-fold
enriched for cells capable of forming large actively growing colonies
(Seery and Watt, 2000)
(Fig. 3).
|
Interpapillary basal layer cells are phenotypically primitive
The expression of several cytokeratin (CK) species varies during the
differentiation program of oesophageal keratinocytes
(Takahashi et al., 1995).
Using in situ hybridization, Viaene and Baert have shown that the pattern of
CK mRNA expression is heterogeneous in the oesophageal epithelial basal layer
(Viaene and Baert, 1995
). CK13
protein is produced by differentiating keratinocytes in all endodermderived
stratified squamous epithelia, including the oesophageal epithelium
(Moll et al., 1982
). CK13 mRNA
is present at high levels in the cells of both the PBL and epibasal layers but
is absent from the keratinocytes of the IBL. In addition, the signal intensity
for CK14 and CK15 mRNA is patchy in the IBL, which contrasts with the high
levels of expression of these species in the PBL and epibasal layers.
Furthermore, mRNA for the differentiation marker CK4 is detectable in the
papillary region from the second epibasal layer onwards but does not appear in
the interpapillary region until the third epibasal layer
(Viaene and Baert, 1995
).
Hence, in terms of differentiation markers, IBL cells are the `least
differentiated' cell type in the tissue.
The data discussed above are thus consistent with the idea that keratinocytes of the IBL are stem cells and with a model of the oesophageal epithelium in which stem and transit amplifying cells are contained in distinctive anatomical compartments: the IBL and epibasal layers, respectively (Fig. 4). Why the putative IBL stem cells, in contrast to the epidermal stem cells, express low levels of integrin ß1 is discussed below.
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The oesophageal epithelium has unexpected properties |
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The behavior of epidermal stem cells is independent of interactions with
their underlying stroma. Epidermal keratinocytes can regulate stem cell
proliferative activity and number independently of interactions with the
dermis (Jones et al., 1995;
Watt, 2001
). In contrast, the
basement membrane of the oesophageal epithelium plays a central role in
controlling oesophageal stem cell behavior. Interactions between oesophageal
stem cells and the oesophageal basement membrane determine the asymmetric
orientation of cell division and dictate the overall tissue architecture. When
oesophageal keratinocytes are cultured in vitro on denuded acellular dermis,
the orientation of cell division in the basal layer of the epithelium formed
is random. In addition, this in vitro epithelium is flat and featureless. In
contrast, when oesophageal keratinocytes are cultured on denuded acellular
oesophageal submucosa with intact basement membrane, the orientation of cell
division is predominantly asymmetrical, and an epithelium with prominent
papillae is formed that resembles the in vivo tissue
(Seery and Watt, 2000
).
Recent data from the study of Drosophila embryogenesis suggest a
mechanism by which basement-membrane/adhesion-molecule interactions might
influence the orientation of basal cell division. Lu et al. have shown that
the formation of adherens junctions dictates the orientation of cell division
in Drosophila neuroblasts and neuroepithelial cells. Following
disruption of adherens junctions, neuroepithelial division, which normally
occurs in the plane of the neuroepithelium, becomes asymmetric in orientation
(Lu et al., 2001). In
addition, Le Borgne et al. have shown that cadherin-catenin function in the
single organ precursor cell of Drosophila determines the orientation
of cell division at certain stages in the formation of the dorsal sensory
organ of the thorax (Le Borgne et al.,
2002
). Intracellular adhesion and cadherincatenin levels are
regulated by interactions with the extracellular matrix and in particular by
integrin ligation (Gimond et al.,
1999
). If basement-membrane/adhesion-molecule interactions can
influence the orientation of basal cell division, this might offer an
explanation for the observed difference in the orientation of mitotic cells in
the IBL and PBL. The precise composition of the oesophageal basement membrane
has not been determined, but the levels of at least one laminin isoform (the
ß2 laminin chain) vary between the IBL and PBL
(Seery and Watt, 2000
).
Several molecules have been identified in Drosophila that induce
an asymmetric accumulation of cell-fate determinants during cytokinesis in
embryonic stem cells (e.g. Frizzled, Inscuteable and Bazooka)
(Bellaiche et al., 2001;
Orgogozo et al., 2001
). These
cell-fate determinants (e.g. Numb, an antagonist of Notch signaling) confer
different phenotypes on each daughter cell, thus contributing to the
generation of cellular diversity in the embryo
(Jan and Jan, 2000
).
Functional homologues of these proteins have been described in vertebrates
(Cayouette et al., 2001
). We do
not know if they, or related molecules, play a role in determining the fate of
the progeny of IBL stem cell divisions, because there is no data concerning
their patterns of expression in the oesophagus. In fact, such mechanisms may
not be necessary in keratinocytes. In common with their epidermal equivalents,
oesophageal keratinocytes differentiate in suspension culture
(Adams and Watt, 1989
;
Dazard et al., 2000
;
Seery and Watt, 2000
). Hence,
following asymmetric mitosis in the IBL, loss of contact with the basement
membrane eventually triggers terminal differentiation in the epibasal daughter
cell and its progeny. Thus, by determining the orientation of cell division in
the IBL, basement-membrane/adhesion-molecule interactions may also determine
the fate of the daughter cells produced.
The idea that basement membrane components in the IBL somehow provide a `stem cell niche' is in keeping with the prevailing situation throughout the rest of the gastrointestinal tract. Regional variation along the crypt-villus axis in laminin components of the basement membrane plays the central role in establishing stem cell identity in the columnar-lined gastrointestinal tract (Simon-Assman et al., 1998).
Invariant stem cell division might seem inflexible for situations of
increased cell need. However, cell divisions that are symmetrical relative to
the underlying basement membrane are occasionally observed in the IBL
(Seery and Watt, 2000).
Whether the ratio of symmetrical to asymmetrical divisions in the IBL can be
altered by signals from the surrounding tissue is not known. Cells in the IBL
have a characteristic morphology during S phase
(Seery and Watt, 2000
). The
cell remains attached to the basement membrane by a thin film of cytoplasm,
but its nucleus is displaced into the epibasal layers. Such a morphology is
reminiscent of the intermitotic nuclear migration during stem cell division in
the neuroepithelium (Alvarez-Buylla et al.,
1998
). Jan and Jan have suggested that intermitotic nuclear
migration allows stem cells to receive signals from the surrounding tissue
that dictate asymmetric partitioning of molecules and consequently determine
the orientation of cell division (Jan and
Jan, 2000
). If such signals can alter the balance of symmetrical
and asymmetrical mitoses in the IBL, this should offer a novel mechanism for
controlling the balance between stem cell and transit amplifying cell
production. By altering stem cell numbers, such a mechanism would have marked
effects on the rate of new cell production in the tissue
(Potten and Morris, 1988
;
Morrison et al., 1997
).
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Many questions to answer |
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The status of the cells in the PBL is difficult to define in terms of the
stem/transit-amplifying-cell model. In terms of in vivo proliferation and CK
mRNA expression pattern, the cells of this region appear to be intermediate
between the putative stem cells of the IBL and the putative transit amplifying
cells of the epibasal layers (Seery and
Watt, 2000; Viaene and Baert,
1995
). Interestingly, the in vitro clonogenicity of basal
epidermal keratinocytes varies linearly with integrin expression levels. There
might thus be a continuum of cellular behavior in the proliferative zone of
the epidermis rather than strictly defined populations of stem cells and
transit amplifying cells. A similar situation may apply in the oesophageal
epithelium, PBL cells being functionally intermediate between these two cell
types. However, no data defining the lineage relationship between the cells of
the IBL and the PBL are yet available, and the model outlined in
Fig. 4 makes no prediction
about this relationship. The hypothesis that the papillae are formed by
sideways expansion of cells in the IBL remains a possibility
(Jankowski et al., 1992b
). The
progency of the rare divisions parallel to the basement membrane in this site
could contribute to the PBL (Seery and
Watt, 2000
). In the epidermis, interactions between Delta1
expressed on the surface of cells in the `integrin bright' stem cell cluster
and Notch1 on surrounding cells are important in controlling stem cell
activity. Interaction between Delta1 and Notch1 promotes cellular
differentiation at the edges of the stem cell clusters, thus maintaining the
anatomical integrity and size of the stem cell compartment
(Lowell et al., 2000
).
Whether, such interactions at the junction of the IBL and PBL play a role in
controlling their relative size and composition is unknown. The pattern of
expression of Notch and Delta in the oesophagus has not been described in
detail.
The model in Fig. 4 takes no
account of the glandular structures associated with the oesophageal
epithelium. Tubuloalveolar glands are present in the submucosa along the
length of the oesophagus. Ducts connecting these glands to the luminal surface
are lined by a cuboidal epithelium that becomes stratified in its terminal
part (Hopwood et al., 1986).
Gillen et al. suggested that reconstitution of the surface epithelium from
stem cells in the tubuloalveolar glands, following mucosal injury, is the
source of Barrett's oesophagus (vide infra)
(Gillen et al., 1988
).
Although there is no direct evidence for the presence of a stem cell
population in these glands, their existence would not necessarily conflict
with the model discussed here and would, in fact, allow an interesting analogy
to be drawn with the epidermis. In the epidermis, stem cells appear to reside
not only in the interfollicular epithelium but also in the epidermal
appendages, specifically in the bulge region of the hair follicle
(Cotsarelis et al., 1990
;
Rochat et al., 1994
;
Panteleyev et al., 2001
). The
detailed histological and functional analyses carried out on the cell biology
of the hair follicle have not been applied to the study of the glandular
structures of the oesophagus. This is an area of study of considerable
clinical importance.
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Oesophageal stem and transit amplifying cells in disease |
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With regard to the hypothesized origin of Barrett's oesophagus from stem
cells in the tubuloalveolar glands, note that duodenogastric reflux can
trigger a similar transdifferentiation in the oesophagus of rats
(Pera et al., 2000). Because
rats do not have glandular structures in the oesophagus, this indicates that,
at least in this species, the differentiation program of keratinocytes can be
modified by GORD to induce columnar differentiation. Furthermore, as gastric
refluxate is not genotoxic (Fein et al.,
2000
), it is possible that the effect of gastroesophageal reflux
on oesophageal transdifferentiation represents an epigenetic effect on
post-mitotic cells rather than an abnormality of stem cells. In this regard,
it is of interest that bile salts exert regulatory effects on cellular
differentiation in the haemopoietic system through effects on transcriptional
regulatory pathways (Zimber et al.,
2000
). Interestingly, it has recently been shown that components
of the Wnt signaling pathway play a key role controlling the balance between
squamous and glandular differentiation in epidermal cells
(Arnold and Watt, 2001
; Merril
et al., 2001; Miyoshi et al.,
2002
; Niemann et al.,
2002
). Although abnormalities in Ecadherin and catenin signaling
have been implicated in the progression of Barrett's oesophagus to
adenocarcinoma (Bailey et al.,
1998
; Seery et al.,
1999
), the role of these pathways in the primary pathogenesis of
Barrett's metaplasia has not been determined.
That gastroesophageal refluxate can influence transit amplifying cell
differentiation in the oesophagus is illustrated by the effects of GORD on
oesophageal epithelial morphology. Although oesophageal keratinocytes
differentiate when held in suspension
(Seery and Watt, 2000), the
putative transit amplifying cells of the epibasal layers seem to be capable of
initiating a program of differentiation, as evidenced by expression of several
differentiation markers, and to continue proliferating in vivo. Furthermore,
the relative rates of the two processes seem to be affected by GORD, because
the relative thickness of all the layers described in
Fig. 1 varies in this disorder.
In the presence of GORD, an unidentified proliferative stimulus results in
marked expansion of the transit amplifying population, with elongation of the
papillae, thickening of the epibasal layers and thinning of the differentiated
zone (Livstone et al.,
1977
).
Given that the methods of oesophageal keratinocyte isolation and culture described in this commentary result in little contamination with glandular elements, it may now be possible to dissect in vitro the role of genetic and epigenetic factors in controlling oesophageal keratinocyte differentiation and proliferation.
The oesophageal epithelium is worthy of further study. The combination of readily defined stem and transit amplifying components, the clinical importance of primary diseases of oesophageal keratinocytes and the ease of their in vitro culture is unique among adult epithelia.
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Acknowledgments |
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References |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adams, J. C. and Watt, F. M. (1989). Fibronectin inhibits terminal differentiation of human keratinocytes. Nature 340,307 -309.[Medline]
Alvarez-Buylla, A., Garcia-Verduga, J. M., Matro, A. S. and
Merchant-Larios, H. (1998). Primary neural precursors and
intermitotic nuclear migration in the ventricular zone of adult canaries.
J. Neurosci. 18,1020
-1037.
Arnold, I. and Watt, F. M. (2001). c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr. Biol. 11,558 -568.[Medline]
Bailey, T., Biddlestone, L., Shepherd, N., Barr, H., Warner, P. and Jankowski, J. A. (1998). Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation. Am. J. Pathol. 152,135 -144.[Abstract]
Behar, J. and Sheahan, D. G. (1975). Histological abnormalities in reflux esophagitis. Arch. Pathol. 99,387 -391.[Medline]
Bellaiche, Y., Gho, M., Kaltschmidt, J. A., Brand, A. H. and Schweisguth, F. (2001). Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division. Nat. Cell Biol. 3, 50-57.[Medline]
Cayouette, M., Whitmore, A. V., Jeffery, G. and Raff, M.
(2001). Asymmetric segregation of Numb in retinal development and
the influence of the pigmented epithelium. J.
Neurosci. 21,5643
-5651.
Cotsarelis, G., Sun, T.-T. and Lavker, R. M. (1990). Label-retaining cells reside in the bulge area of the pilosebaceous unit: implications for follicular stem cells, hair cycle and skin carcinogenesis. Cell 61,1329 -1337.[Medline]
Dazard, J. E., Piette, J., Basset-Seguin, N., Blanchard, J. M. and Gandarillas, A. (2000). Switch from p53 to MDM2 as differentiating human keratinocytes lose their proliferative potential and increase in cellular size. Oncogene 19,3693 -3705.[Medline]
Devesa, S. S., Blot, W. J. and Fraumeni, J. F. (1998). Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83,2049 -2053.[Medline]
Fein, M., Fuchs, K. H., Stopper, H., Diem, S. and Herderich,
M. (2000). Duodenogastric reflux and foregut carcinogenesis:
analysis of duodenal juice in a rodent model of cancer.
Carcinogenesis 21,2079
-2084.
Geboes, K. and Desmet, V. (1978). Histology of the esophagus. Front. Gastrointest. Res. 3, 1-17.[Medline]
Gillen, P., Keeling, P., Byrne, P. J., West, A. B. and Hennessy, T. P. (1988). Experimental columnar metaplasia in the canine oesophagus. Br. J. Surg. 75,113 -115.[Medline]
Gimond, C., van der Flier, A., van Delft, S., Brakebusch, C.,
Kuikman, I., Collard, J. G., Fassler, R. and Sonnenberg, A.
(1999). Induction of cell scattering by expression of ß1
integrins in ß1-deficient epithelial cells requires activation of members
of the Rho family of GTPases and downregulation of cadherin and catenin
function. J. Cell Biol.
147,1325
-1340.
Hall, P. A. and Watt, F. M. (1989). Stem cells: the generation and maintenance of cellular diversity. Development 106,619 -633.[Medline]
Hopwood, D., Coghill, G. and Sanders, D. S. A. (1986). Human oesophageal submucosal glands. Histochemistry 86,107 -112.[Medline]
Ismail-Beigi, F., Horton, P. F. and Pope, C. E., II (1970). Histological consequences of gastroesophageal reflux in man. Gastroenterol. 58,163 -174.[Medline]
Jan, Y. N. and Jan, L. Y. (2000). Polarity in cell division: what frames thy fearful asymmetry. Cell 100,599 -602.[Medline]
Jankowski, J., Hopwood, D. and Wormsley, K. G. (1992a). Flow cytometric analysis of growth regulatory peptides in Barrett's oesophagus. Scand. J. Gastroenterol. 27,147 -154.[Medline]
Jankowski, J., Austin, W., Howat, K., Coghill, G., Hopwood, D., Dover, R. and Wormsley, K. G. (1992b). Proliferating cell nuclear antigen in oesophageal mucosa: comparison with autoradiography. Eur. J. Gastroenterol. Hepatol. 4, 579-584.
Jankowski, J., Hopwood, D., Dover, R. and Wormsley, K. G. (1993). Development and growth of normal, metaplastic and dysplastic oesophageal mucosa: biological markers of neoplasia. Eur. J. Gastroenterol. Hepatol. 5, 235-246.
Jensen, U. B., Lowell, S. and Watt, F. M.
(1999). The spatial relationship between stem cells and their
progeny in the basal layer of the human epidermis: a new view based on
whole-mount labeling and lineage analysis. Development
126,2409
-2418.
Jones, P. H., Harper, S. and Watt, F. M. (1995). Stem cell patterning and fate in the human epidermis. Cell 80,83 -93.[Medline]
Jones, P. H. and Watt, F. M. (1993). Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73,713 -724.[Medline]
Le Borgne, R., Bellaiche, Y. and Schweisguth, F. (2002). Drosophila Ecadherin regulates the orientation of asymmetric cell division in the sensory organ lineage. Curr. Biol. 12,95 -104.[Medline]
Livstone, E. M., Sheahan, D. G. and Behar, J. (1977). Studies of esophageal epithelial cell proliferation in patients with reflux esophagitis. Gastroenterol. 73,1315 -1319.[Medline]
Lowell, S., Jones, P., Le Roux, I., Dunne, J. and Watt, F. M. (2000). Stimulation of human epidermal differentiation by delta-notch signaling at the boundaries of stem cell clusters. Curr. Biol. 10,491 -500.[Medline]
Lu, B., Roegiers, F., Jan, L. Y. and Jan, Y. N. (2001). Adherens junctions inhibit asymmetric division in the Drosophila neuroepithelium. Nature 409,522 -525.[Medline]
Merrill, B. J., Gat, U., DasGupta, R. and Fuchs, E.
(2001). Tcf3 and Lef1 regulate lineage differentiation of
multipotent stem cells in skin. Genes Dev.
15,1688
-1705.
Miyoshi, K., Shillingford, J. M., Le Provost, F., Gounari, F.,
Bronson, R., von Boehmer, H., Taketo, M. M., Cardiff, R. D., Hennighausen, L.
and Khazaie, K. (2002). Activation of beta-catenin signaling
in differentiated mammary secretory cells induces transdifferentiation into
epidermis and squamous metaplasias. Proc. Natl. Acad. Sci.
USA 99,219
-224.
Moles, J. P. and Watt, F. M. (1997). The
epidermal stem cell compartment: variation in expression levels of E-cadherin
and catenins within the basal layer of human epidermis. J.
Histochem. Cytochem. 45,867
-874.
Moll, R., Franke, W. W. and Schiller, D. L. (1982). The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31, 11-24.[Medline]
Morrison, S. J., Shah, N. M. and Anderson, D. J. (1997). Regulatory mechanisms in stem cell biology. Cell 88,287 -298.[Medline]
Niemann, C., Owens, D. M., Hulsken, J., Birchmeier W. and Watt,
F. M. (2002). Expression of DeltaNLef1 in mouse epidermis
results in differentiation of hair follicles into squamous epidermal cysts and
formation of skin tumours. Development
129,95
-109.
Orgogozo V., Schweisguth, F. and Bellaiche Y.
(2001). Lineage, cell polarity and inscuteable function in the
peripheral nervous system of the Drosophila embryo.
Development 128,631
-643.
Panteleyev, A. A., Jahoda, C. A. and Christiano, A. M.
(2001). Hair follicle predetermination. J. Cell
Sci. 114,3419
-3431.
Pera, M., Brito, M. J., Poulsom, R., Riera, E., Grande, L.,
Hanby, A. and Wright, N. A. (2000). Duodenal-content reflux
esophagitis induces the development of glandular metaplasia and adenosquamous
carcinoma in rats. Carcinogenesis
21,1587
-1591.
Potten, C. S. and Morris, R. J. (1988). Epithelial stem cells in vivo. J. Cell. Sci. Suppl. 10, 45-62.[Medline]
Rheinwald, J. G. and Green, H. (1975). Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 6, 331-343.[Medline]
Richter, J. E. (2001). Importance of bile reflux in Barrett's esophagus. Dig. Dis. 18,208 -216.
Rikimura, K., Moles, J. P. and Watt, F. M. (1997). Correlation between hyperproliferation and suprabasal integrin expression in human epidermis reconstituted in vitro. Exp. Dermatol. 6,214 -221.[Medline]
Rochat, A., Kobayashi, K. and Barrandon, Y. (1994). Location of stem cells of human hair follicles by clonal analysis. Cell 76,1063 -1073.[Medline]
Seery, J. P., Syrigos, K. N., Karayiannakis, A. J., Valizadeh, A. and Pignatelli, M. (1999). Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. Acta Oncol. 38,945 -948.[Medline]
Seery, J. P. and Watt, F. M. (2000). Asymmetric stem-cell divisions define the architecture of the human oesophageal epithelium. Curr. Biol. 10,1447 -1450.[Medline]
Simon-Assmann, P., Lefebvre, O., Bellissent-Waydelich, A.,
Olsen, J., Orian-Rousseau, V. and De Arcangelis, A. (1998).
The laminins: a role in intestinal morphogenesis and differentiation.
Ann. NY Acad. Sci. 859,46
-64.
Takahashi, H., Sikata, N., Senzaki, H., Shintaku, M. and Tsubura, A. (1995). Immunohistochemical staining patterns in normal oesophageal epithelium and carcinoma of the oesophagus. Histopathol. 26,45 -50.[Medline]
Viaene, A. I. and Baert, J. H. (1995). Expression of cytokeratin mRNAs in normal human esophageal epithelium. Anat. Record 241,88 -98.[Medline]
Vogel, G. (2000). Can old cells learn new
tricks? Science 287,1418
-1419.
Watt, F. M. (2001). Stem cell fate and patterning in mammalian epidermis. Curr. Opin. Gen. Dev. 11,410 -417.[Medline]
Watt, F. M. and Hogan, B. L. (2000). Out of
Eden: stem cells and their niches. Science
287,1427
-1430.
Zimber, A., Chedeville, A., Abita, J. P., Barbu, V. and Gespach,
C. (2000). Functional interactions between bile acids, all
trans retinoic acid and 1,25-dihydroxy-vitamin D3 on monocytic differentiation
and myeloblastin gene down-regulation in HL60 and THP-1 human leukemia cells.
Cancer Res. 60,672
-678.
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