Human dermal stem cells differentiate into functional epidermal melanocytes

Li, Ling; Fukunaga-Kalabis, Mizuho; Yu, Hong; Xu, Xiaowei; Kong, Jun; Lee, John Tayu; Herlyn, Meenhard

doi:10.1242/jcs.061598

Cited by 153 publications

(169 citation statements)

References 31 publications

(40 reference statements)

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“…Since the first identification of hematopoietic stem cells, similar cells of mesodermal, ectodermal, and endodermal lineages have been recognized in adult tissues. In skin, for instance, epithelial stem cells have been found in the basal layer of the epidermis and in the bulge or 'wulst' region of hair follicles, 5 mesenchymal stem cells are scattered within the dermis, 6 and melanocytic progenitors are present in dermis 7 and hair follicles. 8 These adult stem cells are relatively rare, give rise to cells of the tissue type in which they are found, and function in tissue repair and maintenance as well as potentially in regenerative responses.…”

Section: What Is a 'Stem Cell'?mentioning

confidence: 99%

Melanoma stem cells: not rare, but well done

Girouard

Murphy

2011

Laboratory Investigation

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Since the identification of self-renewing cells in the hematopoietic system, stem cells have transformed the study of medicine. Cancer biologists have identified stem-like cells in multiple malignancies, including those of solid organs. This has led to the development of a stem cell theory of cancer, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorigenesis. This contrasts with the stochastic model of tumor development, which advances that all tumor cells are capable of tumor formation. Within the field of melanoma, the identity and existence of cancer stem cells has been the subject of recent debate. Much of the controversy may be traced to differences in interpretations and definitions related to the cancer stem cell theory, and the use of dissimilar methodologies to study melanoma cells. Accumulating evidence suggests that cancer stem cells may exist in melanoma, although their frequency may vary and they may be capable of phenotypic plasticity. Importantly, these primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but also may confer virulence via immune evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of melanoma stem cells and the pathways that endow them with virulence hold promise for the design of more effective strategies for amelioration and eradication of this most lethal form of skin cancer.

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Section: What Is a 'Stem Cell'?mentioning

confidence: 99%

Melanoma stem cells: not rare, but well done

Girouard

Murphy

2011

Laboratory Investigation

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“…These results suggest that MSCs and/or their immediate progenies, such as AMMCs, exist not only in the bulge region of HFs but also within the epidermis or dermis of glabrous skin [17][18][19][20]. These MSCs provide a new basis to understand the pathological changes caused by defects or dysfunction in stem cells, such as hair graying, vitiligo and melanoma [10,15,19].…”

Section: Discussionmentioning

confidence: 93%

“…Some authors have hypothesized that human extra follicular skin contains a stem cell population, called human DSCs, which are capable of differentiating into a wide variety of cell types, such as MCs [17,19]. It has been suggested that DSCs may be a source of extra follicular epidermal MCs [20].…”

Section: Discussionmentioning

confidence: 99%

The Clonal Growth Behavior of Melanocytes Derived From Melanocyte Stem Cells in Glabrous Skin

Zhang¹,

Liu²,

Cheng³

et al. 2017

JDC

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Melanocyte stem cells (MSCs) play crucial roles in the pigmentation of human skin and hair, but methods to isolate and culture them are not well characterized. In our study, we cultured melanocytes derived from human fetal hair follicles and from glabrous adult foreskins. Three kinds of culture methods were employed, namely, via conventional enzyme digestion and cultivation, culture on a matrigel matrix and tissue culture. The results show that a special population of melanocytes occurred in primary cultures, which differed from mature epidermal melanocytes. Those cells displayed bipolar or tripolar phenotypes, proliferated very rapidly and their growth patterns resembled schools of fishes. Immunohistochemical staining with the HMB-45 antibody confirmed that these cells were indeed melanocytes. We speculate that these melanocytes in clone-like growth patterns may have derived from MSCs or their progenies, which exist not only in the bulge region of hair follicles but also within the epidermis and/or dermis of glabrous skin.

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“…Quantitative analyses can be performed on this model by measuring the depth of invasion and the extent of proliferation. In addition to characterization of normal and malignant melanocytic cells, using the model we can directly induce the differentiation of dermal stem cells into matured melanocytes, which home to the basal layer of epidermis and establish bona fide communication with keratinocytes through upregulation of E-cadherin (6).…”

Section: Discussionmentioning

confidence: 99%

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Fukunaga-Kalabis

Herlyn

2011

JoVE

Self Cite

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Citation: Li, L., Fukunaga-Kalabis, M., Herlyn, M. The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression. J. Vis. Exp. (54), e2937, doi:10.3791/2937 (2011. AbstractMost in vitro studies in experimental skin biology have been done in 2-dimensional (2D) monocultures, while accumulating evidence suggests that cells behave differently when they are grown within a 3D extra-cellular matrix and also interact with other cells (1-5). Mouse models have been broadly utilized to study tissue morphogenesis in vivo. However mouse and human skin have significant differences in cellular architecture and physiology, which makes it difficult to extrapolate mouse studies to humans. Since melanocytes in mouse skin are mostly localized in hair follicles, they have distinct biological properties from those of humans, which locate primarily at the basal layer of the epidermis. The recent development of 3D human skin reconstruct models has enabled the field to investigate cell-matrix and cell-cell interactions between different cell types. The reconstructs consist of a "dermis" with fibroblasts embedded in a collagen I matrix, an "epidermis", which is comprised of stratified, differentiated keratinocytes and a functional basement membrane, which separates epidermis from dermis. Collagen provides scaffolding, nutrient delivery, and potential for cell-to-cell interaction. The 3D skin models incorporating melanocytic cells recapitulate natural features of melanocyte homeostasis and melanoma progression in human skin. As in vivo, melanocytes in reconstructed skin are localized at the basement membrane interspersed with basal layer keratinocytes. Melanoma cells exhibit the same characteristics reflecting the original tumor stage (RGP, VGP and metastatic melanoma cells) in vivo. Recently, dermal stem cells have been identified in the human dermis (6). These multi-potent stem cells can migrate to the epidermis and differentiate to melanocytes.

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Human dermal stem cells differentiate into functional epidermal melanocytes

Cited by 153 publications

References 31 publications

Melanoma stem cells: not rare, but well done

Melanoma stem cells: not rare, but well done

The Clonal Growth Behavior of Melanocytes Derived From Melanocyte Stem Cells in Glabrous Skin

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

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