Location of proliferating cells in human epidermis

Penneys, N. S.

doi:10.1001/archderm.101.3.323

Cited by 35 publications

(14 citation statements)

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“…10). This explains the presence of binucleated cells that we have detected in epidermis and previously reported mitotic figures in peribasal layers that remained unexplained [10], [11], [12]. Mitotic figures were not observed in more superficial layers.…”

Section: Discussionsupporting

confidence: 77%

“…Traditionally, proliferative keratinocytes have been assumed to exit the cell cycle into G0 (cell growth arrest) before they initiate terminal differentiation. This model however does not explain a growing body of evidence: i) keratinocytes grow in size during differentiation [7], [8], [9]; ii) some unexplained mitotic figures or thymidine-incorporating cells have been reported in the peribasal layer [10], [11], [12], [13], [14]; iii) inhibiting keratinocytes entry in cell cycle did not provoke terminal differentiation in a variety of studies [15]; for instance, over-expression of the cell cycle inhibitor p21CIP rather inhibited differentiation [16], [17]; iv) a temporal gap between keratinocyte cell cycle arrest and terminal differentiation has not been observed [13], [15], [18]; v) primary keratinocytes can differentiate terminally from any phase of the cell cycle and differentiating cells are not predominantly in G0/G1 but rather they accumulate in G2/M [19]; vi) constitutive activation of the cell cycle inducer, proto-oncogene Myc in human keratinocytes or mouse epidermis stimulates differentiation [20], [21], [22]; vii) finally and not less important, benign hyperproliferative lesions of skin consistently associate epidermal hyperplasia with hyperkeratosis (thickening of the differentiated strata), as it occurs in a variety of transgenic mouse lines over-expressing cell cycle molecules in epidermis including E2F [23], cyclin D1 [24], [25], MDM2 [26], cdk4 [27] or cdk2 [28]. Therefore, a good amount of evidence suggests that epidermal differentiation does not require cell cycle arrest.…”

Section: Introductionmentioning

confidence: 98%

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A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

et al. 2010

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How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 98%

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

et al. 2010

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“…PTTG1 was shown to be expressed in a small fraction of the basal and peribasal keratinocytes, and was localized in the nucleus and cytoplasm (Figure 1a). Some PTTG1-positive keratinocytes were located not in the basal layer but in the peribasal layer, indicating that some peribasal keratinocytes still possessed proliferative capacity and had not completed cell cycle exit, as reported previously (Pinkus and Hunter, 1966;Penneys et al, 1970;Regnier et al, 1986;Dover and Watt, 1987;Bata-Csorgo et al, 1993;Zanet et al, 2010). Next, NMKs were cultured in low-or high-calcium-containing medium.…”

Section: Pttg1 Expression In Normal Keratinocytes Is Under Cell Cyclementioning

confidence: 65%

Pituitary Tumor-Transforming Gene 1 Enhances Proliferation and Suppresses Early Differentiation of Keratinocytes

Ishitsuka

Kawachi

Taguchi

et al. 2012

Journal of Investigative Dermatology

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The epidermis is a self-renewing tissue, the homeostasis of which is dependent upon the tight balance between proliferation and differentiation based on appropriate regulation of the cell cycle. The cell cycle regulation is dependent on the interactions among a number of cell cycle regulatory molecules, including the pituitary tumor-transforming gene 1 (PTTG1), also known as securin, a regulator of sister chromatid separation and transition from metaphase to anaphase. This study was conducted to clarify the less-known functions of PTTG1 in the epidermis by the use of keratinocytes cultured under two-dimensional (2D) or three-dimensional (3D) conditions. Forced overexpression of PTTG1 caused upregulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and c-Myc, resulting in enhanced proliferation and suppression of early differentiation without apparent alterations in terminal differentiation, and the exogenous PTTG1 was downregulated in association with cell cycle exit. In contrast, depletion of PTTG1 caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that PTTG1 could alter the proliferation status by modulating the expression levels of the other cell cycle regulatory proteins, and excess PTTG1 primarily affects early differentiation of keratinocytes under the stability regulation associated with cell cycle exit.

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“…Proliferating cells are found in the basal and suprabasal compartments of the epidermis. It has been noted that skin injury is an inductor of hyperproliferative cellular states 40 and that HA suppresses epidermal differentiation in organotypic cultures 36 and is involved and support keratinocyte proliferation. 35 Typically, keratinocyte proliferation is associated with the second phase of re-epithelization.…”

Section: Proliferationmentioning

confidence: 99%

Improved Preservation of the Tissue Surrounding Percutaneous Devices by Hyaluronic Acid and Dermatan Sulfate in a Human Skin Explant Model

et al. 2009

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Cellular apoptosis and proliferation was analyzed in an in vitro culture system of organotypic human skin explants in the presence or absence of external fixator pins. The effect on the tissues of a mixture of hyaluronic acid and dermatan sulfate (HA+DS) delivered at the skin-pin interface was also studied. After 2 weeks in culture, skin specimens interfaced with fixator pins showed increased keratinocyte apoptosis and proliferation compared to specimens without fixator pins. Simultaneously, a relative reduction of apoptosis and proliferation was observed in specimens treated with the HA+DS mixture, regardless of fixation pin presence. In addition, the HA+DS mixture appeared to help in the preservation of the epidermal basal membrane. It is concluded that in this in vitro model, fixator pins induce keratinocyte apoptosis and hyperproliferation, which are reduced in the presence of the HA+DS mixture. These methods may be useful for a better maintenance of the soft tissue surrounding percutaneous devices in vivo.

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Location of proliferating cells in human epidermis

Cited by 35 publications

References 0 publications

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

Pituitary Tumor-Transforming Gene 1 Enhances Proliferation and Suppresses Early Differentiation of Keratinocytes

Improved Preservation of the Tissue Surrounding Percutaneous Devices by Hyaluronic Acid and Dermatan Sulfate in a Human Skin Explant Model

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