Cell Proliferation in Normal Epidermis

Weinstein, Gerald D.; McCullough, Jerry L.; Ross, Priscilla

doi:10.1111/1523-1747.ep12261462

Cited by 156 publications

(109 citation statements)

References 25 publications

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“…The intricate balance of ROS and overall reduction of oxidative stress is extraordinarily important in heart tissue, as the cells that make up the heart have been estimated to have a renewal rate of 1% or less, depending on age (15). This is considerably less than most other organs and tissues, especially the skin, which has shown to have a turnover rate of 39 days for the entire tissue (189).…”

Section: Heart Diseasementioning

confidence: 99%

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Wilking

Ndiaye²,

Mukhtar³

et al. 2013

Antioxidants & Redox Signaling

238

192

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Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful.

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Section: Heart Diseasementioning

confidence: 99%

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Wilking

Ndiaye²,

Mukhtar³

et al. 2013

Antioxidants & Redox Signaling

238

192

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“…Although many of the basal cells are capable of multiplication (1), few of them are thought to be self-renewing stem cells (2)(3)(4).…”

mentioning

confidence: 99%

Three clonal types of keratinocyte with different capacities for multiplication.

Barrandon¹,

Green²

1987

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

1,183

1,083

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Colony-forming human epidermal cells are heterogeneous in their capacity for sustained growth. Once a clone has been derived from a single cell, its growth potential can be estimated from the colony types resulting from a single plating, and the clone can be assigned to one of three classes. The holoclone has the greatest reproductive capacity: under standard conditions, fewer than 5% of the colonies formed by the cells of a holoclone abort and terminally differentiate. The paraclone contains exclusively cells with a short replicative lifespan (not more than 15 cell generations), after which they uniformly abort and terminally differentiate. The third type of clone, the meroclone, contains a mixture of cells of different growth potential and is a transitional stage between the holoclone and the paraclone. The incidence of the different clonal types is affected by aging, since cells originating from the epidermis of older donors give rise to a lower proportion of holoclones and a higher proportion of paraclones.The epidermis is a stratified squamous epithelium whose differentiated cells are the progeny of proliferative cells located mainly in the basal cell layer. Although many of the basal cells are capable of multiplication (1), few of them are thought to be self-renewing stem cells (2-4). We have recently shown that the clone-forming ability of a human keratinocyte in culture can be estimated from its size: small keratinocytes give rise to clones with high frequency, larger ones do so with lower frequency, and still larger ones, not at all. But once a colony has formed, its growth potential is not specified by the size of the founding cell (5).We describe here a method of analysis that reveals the growth potential of individual clones. We inoculate a single founding cell, and 7 days later we transfer the progeny, while they are still growing exponentially, to indicator dishes, where they are allowed to grow for a further period of 12 days. According to the growth in the indicator dishes, we can classify the original clone. Holoclones (holo = entire) form large rapidly growing colonies; fewer than 5% of the colonies abort and terminally differentiate. Paraclones (para = beyond) are programmed for limited growth and consequently form uniformly small, terminal colonies on the indicator dishes. Meroclones (mero = partial) form two kinds of colonies on the indicator dishes-growing and terminal. The meroclone therefore contains a proportion of cells that have degraded to paraclone-formers. MATERIALS AND METHODSCell Culture. Human epidermal keratinocytes were cultivated as previously described (6), using lethally irradiated supporting 3T3 cells (7). The epidermal growth factor used to promote multiplication (8) was the cloned human polypeptide kindly provided by Chiron (Emeryville, CA) (9). All experiments were carried out with a single batch of serum tested for its ability to support colony formation. The medium was changed every 4 days. Strains AY and YF 19 were derived from foreskin, strain GMA from thigh,...

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“…(i) What cells of the basal and more superficial layer can multiply and what are their division rates (1)(2)(3)(4)? (ii) What fraction of the cells possess sufficient growth potential as to be clonogenic (5)(6)(7)?…”

mentioning

confidence: 99%

“…Although there are protein markers characteristic of basal cells in general (8)(9)(10)(11)(12)(13)(14), there are no such markers by means of which one might discriminate between basal cells that are clonogenic and those that are not. Studies of growth dynamics in the epidermis are difficult to interpret, and there have been differing estimates even for the average cell cycle time of human basal cells (2,3).…”

mentioning

confidence: 99%

Cell size as a determinant of the clone-forming ability of human keratinocytes.

Barrandon¹,

Green²

1985

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

319

217

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Keratinocytes isolated from human epidermis and subsequently cultured may form clones if they are 11 jam or less in diameter but are irreversibly committed to further enlargement and terminal differentiation if they are 12 pum or more in diameter. When a founding cell of 11 ,um or less forms a small rapidly growing clone in culture, the cells of that clone are able to found new colonies even when their diameter is as great as 20 pum. As the clone becomes larger and grows more slowly, the maximal size of its clonogenic cells is reduced toward that of the epidermis. A cultured cell of up to 20 pum in diameter can, when it divides, give rise to clonogenic progeny smaller than itself, thus reversing the process of enlargement. Cells larger than 20 pum cannot divide and therefore cannot be rescued from terminal differentiation. It is concluded that when keratinocytes multiply rapidly, they extend reversibly the maximal size at which they are capable of generating clones into the range usually characteristic of terminally differentiating cells. It is proposed that this mechanism enables the keratinocyte to accommodate an increased rate of multiplication to its need to attain a large size during terminal differentiation.The basal layer of the epidermis contains multiplying keratinocytes. Terminally differentiating progeny leave this layer and enlarge progressively as they move outward through the spinous layer. The size of the cell is related therefore to the degree of its terminal differentiation.Studies of proliferation in the epidermis have been concerned with questions such as the following ones.

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Cell Proliferation in Normal Epidermis

Cited by 156 publications

References 25 publications

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Three clonal types of keratinocyte with different capacities for multiplication.

Cell size as a determinant of the clone-forming ability of human keratinocytes.

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