Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression

Jones, Philip H.; Watt, Fiona M.

doi:10.1016/0092-8674(93)90251-k

Cited by 1,034 publications

(1,096 citation statements)

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“…2A,B). In previous studies, the rapidly proliferating transit amplifying cell population was identified on the basis of decreased adhesion to collagen matrices, as reflected by decreased cell surface ␣ 2 -integrin expression (Jones and Watt, 1993). When transfected keratinocytes were tested for adherence, there was a small but statistically significant decrease in the binding of the HOXB4-transfected cells to either plastic (Fig.…”

Section: Enforced Expression Of Hoxb4 Is Associated With Increased Prmentioning

confidence: 81%

“…Since the basal cell layer, which exhibits strong HOXB4 protein expression, has been shown to contain the highly proliferative transit amplifying cells (Jones and Watt, 1993), we wished to explore the effects of enforced expression of HOXB4 in keratinocytes. A retroviral vector was used to stably transfect cultured human neonatal keratinocytes with a cDNA encoding the HOXB4 protein.…”

Section: Enforced Expression Of Hoxb4 Is Associated With Increased Prmentioning

confidence: 99%

“…Nuclear HOXB4 protein expression was detected within the basal cell layer of developing epidermis and within the bulge region of the hair follicle. Enforced HOXB4 expression in cultured keratinocytes led to cellular changes previously associated with the transit amplifying keratinocyte pool (Jones and Watt, 1993). HOXB4 mRNA and protein are strongly expressed in the proliferating cell nuclear antigen (PCNA) -positive cell layers of a range of tissue samples from hyperproliferative skin condition, including squamous and basal cell cancers.…”

Section: Introductionmentioning

confidence: 99%

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HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Kömüves

Michael

Arbeit

et al. 2002

Developmental Dynamics

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The HOX homeodomain proteins are fundamental regulators of organ and tissue development, where they are thought to function as transcription factors, and HOX gene expression has been associated with numerous types of cancers. Previous studies have demonstrated that enforced expression of the HOXB4 protein transforms cultured fibroblasts and leads to a selective expansion of the hematopoietic stem cell pool, suggesting that this protein might play a role in cellular proliferation. In support of this concept, we now show that enforced expression of HOXB4 in human neonatal keratinocytes results in increased cellular proliferation and colony formation as well as decreased expression of the alpha-2-integrin and CD44 cell surface adhesion molecules. We previously have reported HOXB4 gene expression in the basal and suprabasal layers of developing human skin and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within epidermal basal cells and in hair follicle inner and outer root sheath cells, whereas strong nuclear signals were observed in the bulge region. In adult skin, HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly localized to the intermediate and differentiated cell layers. In contrast to the striking gradient patterns of HOX gene and protein expression previously described in developing spinal cord and limb, HOXB4 protein was uniformly detected in all regions of the fetal and adult skin. Although little HOXB4 signal localized to proliferative cell layers, as marked by proliferating cell nuclear antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein expression substantially overlapped with PCNA-positive cell in a series of samples of hyperproliferative skin. Taken together, these data suggest that nuclear HOXB4 protein may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis.Published 2002 Wiley-Liss, Inc. †

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Section: Enforced Expression Of Hoxb4 Is Associated With Increased Prmentioning

confidence: 81%

Section: Enforced Expression Of Hoxb4 Is Associated With Increased Prmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Kömüves

Michael

Arbeit

et al. 2002

Developmental Dynamics

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“…We then considered that low density plating may not be a suitable method to isolate equine TSPCs and used differential adhesion to fibronectin as a stem cell isolation method, as previously described for epidermal stem cells and cartilage progenitor cells 24, 25. Plating onto substrates precoated with 1 μg/ml fibronectin promoted osteogenic differentiation of TSPCs grown in osteogenic media as assessed by Alizarin Red staining (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We also found that expression of osteogenic and chondrogenic marker genes was not entirely consistent with histological staining techniques for assessing differentiation. Fibronectin has been identified as a suitable substrate to maintain long term self renewal of embryonic stem cells and has been used for isolation of epidermal stem cells and cartilage progenitors 24, 25, 27. Fibronectin was therefore a good candidate ECM substrate for differential isolation of tendon stem cells.…”

Section: Discussionmentioning

confidence: 99%

Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT)

Williamson

Lee

Humphreys

et al. 2015

Journal Orthopaedic Research

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The aim of this study was to characterize stem and progenitor cell populations from the equine superficial digital flexor tendon, an energy‐storing tendon with similarities to the human Achilles tendon, which is frequently injured. Using published methods for the isolation of tendon‐derived stem/progenitor cells by low‐density plating we found that isolated cells possessed clonogenicity but were unable to fully differentiate towards mesenchymal lineages using trilineage differentiation assays. In particular, adipogenic differentiation appeared to be restricted, as assessed by Oil Red O staining of stem/progenitor cells cultured in adipogenic medium. We then assessed whether differential adhesion to fibronectin substrates could be used to isolate a population of cells with broader differentiation potential. However we found little difference in the stem and tenogenic gene expression profile of these cells as compared to tenocytes, although the expression of thrombospondin‐4 was significantly reduced in hypoxic conditions. Tendon‐derived stem/progenitor cells isolated by differential adhesion to fibronectin had a similar differentiation potential to cells isolated by low density plating, and when grown in either normoxic or hypoxic conditions. In summary, we have found a restricted differentiation potential of cells isolated from the equine superficial digital flexor tendon despite evidence for stem/progenitor‐like characteristics. © 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 33:849–858, 2015.

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Keratinocyte Gene Therapy

Vogel

1993

Arch Dermatol

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Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression

Cited by 1,034 publications

References 49 publications

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT)

Keratinocyte Gene Therapy

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