Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes

Abstract

Amniotic epithelial stem cells (AESCs) are considered as potential alternatives to keratinocytes (KCs) in tissue-engineered skin substitutes used for treating skin damage. However, their clinical application is limited since similarities and distinctions between AESCs and KCs remain unclear. Herein, a transcriptomics analysis and functional evaluation were used to understand the commonalities and differences between AESCs and KCs. RNA-sequencing revealed that AESCs are involved in multiple epidermis-associated biological processes shared by KCs and show more similarity to early stage immature KCs than to adult KCs. However, AESCs were observed to be heterogeneous, and some possessed hybrid mesenchymal and epithelial features distinct from KCs. A functional evaluation revealed that AESCs can phagocytose melanosomes transported by melanocytes in both 2D and 3D co-culture systems similar to KCs, which may help reconstitute pigmented skin. The overexpression of TP63 and activation of NOTCH signaling could promote AESC stemness and improve their differentiation features, respectively, bridging the gap between AESCs and KCs. These changes induced the convergence of AESC cell fate with KCs. In future, modified reprogramming strategies, such as the use of small molecules, may facilitate the further modulation human AESCs for use in skin regeneration.

Role of the ABCA4 Gene Expression in the Clearance of Toxic Vitamin A Derivatives in Human Hair Follicle Stem Cells and Keratinocytes

“…This agrees with the estimated value of LC50 for human hair follicle stem cells, which is lower than the value obtained for keratinocytes. Moreover, we observed that at-RAL treatment greatly increased the expression of the ABCA4 gene in keratinocytes and that following at-RAL treatment, the expression of the ABCA4 gene in keratinocytes positively correlated with the expression of the INV gene (marker of differentiation) (Figure 7) and negatively correlated with the KRT5 gene activity, which is a marker of undifferentiated basal stem cells and reflects their proliferative capacity [30]. These results were sustained in concordance with the observation that retinal was transformed into retinoic acid more slowly in non-differentiating keratinocytes than in differentiating ones [31], and only keratinocytes that already committed to terminal differentiation can express an enzymatic system catalyzing the conversion of retinol into retinoic acid.…”

In vitro differentiation of human amniotic epithelial stem cells into keratinocytes regulated by OPN3

“…Epidermis development, stratification and differentiation is a dynamic process, 32 in the future, enhancing the therapeutic potential and developing new clinical protocols are needed for the application of hAESCs‐based strategies in regenerative medicine.…”