Epithelial stem cells

Jones, Philip H.

doi:10.1002/bies.950190808

Cited by 67 publications

(47 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Higher levels of ␤-1 integrin have been ascribed to keratinocytes with characteristics of stem cells (30)(31)(32)(33). Conversely, ectopic expression of ␤-1 integrin in the suprabasal keratinocytes of transgenic mice and in the in vitro reconstructed epidermis has resulted in epidermal alterations resembling psoriatic epidermis, such as keratinocyte hyperproliferation and delayed onset of differentiation (34,35).…”

Section: Resultsmentioning

confidence: 99%

“…In particular, the persistence of lesion-bearing nuclei in basal keratinocytes in reconstructed XP epidermis, but not in normal epidermis, anticipated mutagenic events in the proliferative equivalent of tissue containing stem keratinocytes (33,52). In vitro reconstructed XP epidermis is thus a unique human system allowing the study of epidermal cell fate in the absence of efficient DNA repair, i.e., with high mutagenesis potential (49).…”

Section: In Vitro Reconstructed Xp Epidermis As a Unique Three-dimensmentioning

confidence: 99%

See 1 more Smart Citation

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skininvitro

Bernerd

Asselineau

Vioux

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sun exposure has been clearly implicated in premature skin aging and neoplastic development. These features are exacerbated in patients with xeroderma pigmentosum (XP), a hereditary disease, the biochemical hallmark of which is a severe deficiency in the nucleotide excision repair of UV-induced DNA lesions. To develop an organotypic model of DNA repair deficiency, we have cultured several strains of primary XP keratinocytes and XP fibroblasts from skin biopsies of XP patients. XP skin comprising both a fullthickness epidermis and a dermal equivalent was succesfully reconstructed in vitro. Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced. In addition, the proliferation of XP keratinocytes was more rapid than that of normal keratinocytes. Moreover, increased deposition of cell attachment proteins, ␣-6 and ␤-1 integrins, was observed in the basement membrane zone, and ␤-1 integrin subunit, the expression of which is normally confined to basal keratinocytes, extended into several suprabasal cell layers. Most strikingly, the in vitro reconstructed XP skin displayed numerous proliferative epidermal invasions within dermal equivalents. Epidermal invasion and higher proliferation rate are reminiscent of early steps of neoplasia. Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops. The availability of in vitro reconstructed XP skin provides opportunities for research in the fields of photoaging, photocarcinogenesis, and tissue therapy.three-dimensional skin model ͉ xeroderma pigmentosum ͉ UVB radiation ͉ DNA damage ͉ keratinocyte differentiation

show abstract

Section: Resultsmentioning

confidence: 99%

Section: In Vitro Reconstructed Xp Epidermis As a Unique Three-dimensmentioning

confidence: 99%

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skininvitro

Bernerd

Asselineau

Vioux

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In vitro, a single stem cell can recreate over 150 cell domains resembling stem cell compartments (26). Mutant transit amplifying or suprabasal cells may also be capable of founding clones (23,26,27). The observation of quantized clone sizes indicates that it is the second step, escape from the stem cell compartment, that is rate limiting.…”

Section: ϫ16mentioning

confidence: 99%

“…After a mutation, a mutant cell's clonal expansion would have two steps: (i) proliferation of the mutant stem cell to fill its own EPU, and (ii) subsequent escape from the mutant EPU to colonize or displace an adjacent one. In vitro, a single stem cell can recreate over 150 cell domains resembling stem cell compartments (26). Mutant transit amplifying or suprabasal cells may also be capable of founding clones (23,26,27).…”

Section: ϫ16mentioning

confidence: 99%

Escaping the stem cell compartment: Sustained UVB exposure allows p53 -mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations

Zhang

Remenyik

Zelterman

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

161

View full text Add to dashboard Cite

Once mutated, a single cell must expand into a clone before becoming significant for carcinogenesis. The forces driving clonal expansion and the obstacles that must be overcome are poorly understood. In a genetic mechanism, acquiring a second mutation conferring a proliferative advantage would enable the cell to expand autonomously. If carcinogen exposure instead induced a physiological change, clonal expansion would require the carcinogen's continued presence. To determine which is the case, we studied microscopic clones of keratinocytes mutated in the p53 tumor suppressor gene. Carcinogen exposure was controlled by irradiating mice with 280 -320 nm UV radiation (UVB), sunlight's principal carcinogenic component; expansion of mutant clones was observed in epidermal sheets. p53-mutant clones grew only during chronic UVB exposure. Therefore, clonal expansion was not triggered by a proliferative mutation but was instead continually driven by UVB. Unexpectedly, the clone size distribution showed periodicity with maxima at estimated intervals of 16 ؎ 6 cells, the size of the epidermal proliferating unit in murine dorsal skin. In the absence of UVB, rare ''imprisoned clones'' increased in cell number without increasing in area. We conclude that: stem cell compartments act as physical barriers to clonal expansion of a p53-mutant keratinocyte; a rate-limiting step in clonal expansion is the colonization of an adjacent compartment; and sustained UVB enables the p53-mutant keratinocyte to colonize without incurring an additional mutation.

show abstract

“…Keratinocytes are generated by local stem cells (Jones et al, 1997), from which also Merkel cells derive. The latter express cytokeratins and are connected with keratinocytes by desmosomes, but do not became engaged in the differentiation process leading to keratinization (Moll et al, 1984;Lewis et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Use of periodate-lysine-paraformaldehyde for the fixation of multiple antigens in human skin biopsies

Pieri¹,

Sassoli²,

Romagnoli³

et al. 2010

Eur J Histochem

View full text Add to dashboard Cite

SUMMARYPeriodate-lysine-paraformaldehyde (PLP) has been proposed as a fixative for glycoprotein antigens which should stabilize periodate oxidized polysaccharide chains through lysine mediated crosslinks, either directly or by the intermediation of formaldehyde. In spite of premises and attempts reported in the literature, this fixative has never become popular for the study of membrane antigens of immune system cells, which leads to doubts on its real efficacy. We have addressed this issue in biopsies of human skin and found that PLP followed by cryoprotection with 30% sucrose and cryosectioning, or PLP fixation of isolated epidermal sheets, consistently provided for good preservation of morphology and intense labeling of major histocompatibility complex class II molecules, CD1a, CD4, CD8, E-cadherin, cytokeratins in general, cytokeratin-18 in particular, and bromodeoxyuridine, incorporated by cycling cells in vitro, and for the demonstration of tyrosinase enzyme activity. PLP-fixed, osmicated and epon-embedded epidermal sheets proved as good as sheets fixed 365 with a mixture of formaldehyde and glutaraldehyde for electron microscopic morphological analysis. Also, these sheets were amenable to immunoperoxidase staining of Langerhans cell membrane antigen CD1a and keratinocyte membrane antigen E-cadherin before being osmicated and prepared for electron microscopy. In a parallel paper, we had also shown that oral mucosa biopsies fixed in PLP showed good morphology and immunolabeling of CD54, CD80, CD83 and CD86. Therefore, we conclude that PLP can be proposed as a multi-task fixative for light and electron microscopic analysis of membrane, cytoplasmic and nuclear antigens of immune system cells and keratinocytes.

show abstract

Epithelial stem cells

Cited by 67 publications

References 63 publications

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skininvitro

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skininvitro

Escaping the stem cell compartment: Sustained UVB exposure allows p53 -mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations

Use of periodate-lysine-paraformaldehyde for the fixation of multiple antigens in human skin biopsies

Contact Info

Product

Resources

About