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

Cells, vol. 11, pp. 70

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.

Authors 11

1. Li‐Ping Liu

   Jiangsu University · University of Tsukuba · Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

   Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan

   Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

2. Dongxu Zheng Aachen Department of Human Genetics

   University of Tsukuba · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan

3. Zheng-Fang Xu

   Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Obstetrics and Gynaecology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

4. Hu-Cheng Zhou

   Jiangsu University · Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

   Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

5. Yun-Cong Wang

   Jiangsu University · Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

   Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

6. Hang Zhou

   Jiangsu University · Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

   Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

7. Jian-Yun Ge

   University of Tsukuba · Wuyi University · Wuyi University

   Affiliation as printed

   Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan

   Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China

8. Mi Li

   Jiangsu University · Affiliated Hospital of Jiangsu University

   Affiliation as printed

   Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

   Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

9. Kazunori Akimoto

   Tokyo University of Science

   Affiliation as printed

   Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan

10. Yumei Li corresponding

    Jiangsu University · Affiliated Hospital of Jiangsu University

    Affiliation as printed

    Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

    Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

11. Yun‐Wen Zheng corresponding

    Jiangsu University · University of Tsukuba · Affiliated Hospital of Jiangsu University · Wuyi University · Yokohama City University · Wuyi University

    Affiliation as printed

    Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan

    Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China

    Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China

    School of Medicine, Yokohama City University, Yokohama 236-0004, Kanagawa, Japan