Characterization of Fetal Keratinocytes, Showing Enhanced Stem Cell-Like Properties: A Potential Source of Cells for Skin Reconstruction

Tan, Kenneth K. B.; Salgado, Giorgiana; Connolly, John E.; Chan, Jerry Kok Yen; Lane, E. Birgitte

doi:10.1016/j.stemcr.2014.06.005

Cited by 36 publications

(31 citation statements)

References 53 publications

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“…The observed differences between the speed of growth for fetal cell cultures and adult cell cultures are in accordance with previous data (Tan et al, 2014), which reported that keratinocyte proliferation is faster in fetal cells than it is in adult cells. In our experiment, the fetal culture reached subconfluency in approximately one day, whereas adult cultures needed approximately 10 days to reach subconfluency.…”

Section: Discussionsupporting

confidence: 92%

“…Green et al described that once a considerable number of cells were available through laboratory cell culture, a patient's own keratinocyte mesh was employed successfully for the regeneration of human skin lesions (Green, 2008). However, according to Tan et al (2014), a disadvantage of using the patient's own cells is the long period of time required before a significant sample of cells could be obtained for application (Tan et al, 2014). These authors, therefore, suggest the use of fetal skin cells as a possible substitute for autologous cells.…”

Section: Introductionmentioning

confidence: 99%

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In vitro identification of a stem cell population from canine hair follicle bulge region

et al. 2018

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Skin is an extensive and easily accessible organ possessing various cell types that are constantly renewed. Previous studies have suggested the presence of a stem cell niche at the bulge region of the hair follicle, which contains cells positive for CD200 and CD34. Thus, this study sought to identify these cell populations in canine skin cells using the following methods 1- collecting samples of adult and fetal skin and isolating and culturing these cells using a method of simple enzymatic digestion and 2- testing the cell cultures for CD200 and CD34 in vitro and comparing them with skin tissue samples (in situ). Immunofluorescence results were negative for both CD200 and CD34 in frozen and paraffin embedded tissue, whereas the analysis showed that cultured cells positive for CD34, CD200 and double positive cells could be visualized in different percentages. Additionally, the pluripotency marker OCT4 was positive in the isolated cells. Analysis of CD34, CD200 and OCT4 by RT-qPCR showed that there is expression in fetal and adult cells, although no difference was observed between groups. Our results suggest that bulge stem cells from both fetuses and adult dogs were reported with the use of CD34 and CD200 markers in this study, and further techniques for cell isolation and in vitro cultivation are needed in order to obtain enriched populations of skin stem cells in dogs.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

In vitro identification of a stem cell population from canine hair follicle bulge region

et al. 2018

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“…This contrasted with fetal skin, where YAP and WBP2 were predominantly nuclear in the majority of basal epidermal cells (Fig. 3b), likely reflecting the higher proportion of proliferative keratinocytes in fetal epidermis45. Similarly, nuclear YAP and WBP2 were prominent in the basal layer of embryonic and neonatal mouse IFE (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 85%

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

et al. 2017

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Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2.

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“…These small peripheral AKs lacked intercellular contacts and all were positive for keratin 14 (marker of basal layer), K8 and K19 (markers of simple epithelia), thus indicating the poor differentiation level of the cells ( 29 ). Of note, keratin 19 is present in the fetal epidermis, but not in adult interfollicular epidermal keratinocytes ( 30 ). Keratin 8 is typically paired with keratin 18 and is temporarily present in the developing epidermis and malignant tumors ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Functional differences between neonatal and adult fibroblasts and keratinocytes: Donor age affects epithelial-mesenchymal crosstalk in vitro

Mateu

Živicová

Krejčí

et al. 2016

International Journal of Molecular Medicine

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Clinical evidence suggests that healing is faster and almost scarless at an early neonatal age in comparison with that in adults. In this study, the phenotypes of neonatal and adult dermal fibroblasts and keratinocytes (nestin, smooth muscle actin, keratin types 8, 14 and 19, and fibronectin) were compared. Furthermore, functional assays (proliferation, migration, scratch wound closure) including mutual epithelial-mesenchymal interactions were also performed to complete the series of experiments. Positivity for nestin and α smooth muscle actin was higher in neonatal fibroblasts (NFs) when compared with their adult counterparts (adult fibroblasts; AFs). Although the proliferation of NFs and AFs was similar, they significantly differed in their migration potential. The keratinocyte experiments revealed small, poorly differentiated cells (positive for keratins 8, 14 and 19) in primary cultures isolated from neonatal tissues. Moreover, the neonatal keratinocytes exhibited significantly faster rates of healing the experimentally induced in vitro defects in comparison with adult cells. Notably, the epithelial/mesenchymal interaction studies showed that NFs in co-culture with adult keratinocytes significantly stimulated the adult epithelial cells to acquire the phenotype of small, non-confluent cells expressing markers of poor differentiation. These results indicate the important differences between neonatal and adult cells that may be associated with improved wound healing during the early neonatal period.

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Characterization of Fetal Keratinocytes, Showing Enhanced Stem Cell-Like Properties: A Potential Source of Cells for Skin Reconstruction

Cited by 36 publications

References 53 publications

In vitro identification of a stem cell population from canine hair follicle bulge region

In vitro identification of a stem cell population from canine hair follicle bulge region

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

Functional differences between neonatal and adult fibroblasts and keratinocytes: Donor age affects epithelial-mesenchymal crosstalk in vitro

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