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Liu LP, Zheng DX, Xu ZF, et al. Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes. Cells. 2021;11(1)doi: 10.3390/cells11010070.
Liu, L. P., Zheng, D. X., Xu, Z. F., Zhou, H. C., Wang, Y. C., Zhou, H., Ge, J. Y., Sako, D., Li, M., Akimoto, K., Li, Y. M., & Zheng, Y. W. (2021). Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes. Cells, 11(1), . https://doi.org/10.3390/cells11010070
Liu, Li-Ping, et al. "Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes." Cells vol. 11,1 (2021). doi: https://doi.org/10.3390/cells11010070
Liu LP, Zheng DX, Xu ZF, Zhou HC, Wang YC, Zhou H, Ge JY, Sako D, Li M, Akimoto K, Li YM, Zheng YW. Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes. Cells. 2021 Dec 27;11(1). doi: 10.3390/cells11010070. PMID: 35011631; PMCID: PMC8750621.
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Cells. 2021 Dec 27;11(1). doi: 10.3390/cells11010070.

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

Cells

Li-Ping Liu, Dong-Xu Zheng, Zheng-Fang Xu, Hu-Cheng Zhou, Yun-Cong Wang, Hang Zhou, Jian-Yun Ge, Daisuke Sako, Mi Li, Kazunori Akimoto, Yu-Mei Li, Yun-Wen Zheng

Affiliations

  1. Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China.
  2. Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
  3. Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan.
  4. Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
  5. Department of Obstetrics and Gynaecology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
  6. Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China.
  7. Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
  8. School of Medicine, Yokohama City University, Yokohama 236-0004, Kanagawa, Japan.

PMID: 35011631 PMCID: PMC8750621 DOI: 10.3390/cells11010070

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.

Keywords: TP63; amniotic epithelial stem cells; cell fate; keratinocytes; mesenchymal; reprogramming; skin regeneration; skin substitutes; stemness; transcriptomics

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