2. Academic Validation
  3. Chemical conversion of human epidermal stem cells into intestinal goblet cells for modeling mucus-microbe interaction and therapy

Chemical conversion of human epidermal stem cells into intestinal goblet cells for modeling mucus-microbe interaction and therapy

  • Sci Adv. 2021 Apr 14;7(16):eabb2213. doi: 10.1126/sciadv.abb2213.
Andong Zhao 1 2,  Hua Qin 1 3,  Mengli Sun 1 3,  Mao Tang 2,  Jinyu Mei 2,  Kui Ma 1,  Xiaobing Fu 4 3 5
Affiliations

Affiliations

  • 1 Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Division and 4th Medical Center, PLA General Hospital and PLA Medical College, 28 Fu Xing Road, Haidian District, Beijing 100853, China.
  • 2 Tianjin Medical University, Tianjin 300070, China.
  • 3 PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing 100048, China.
  • 4 Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Division and 4th Medical Center, PLA General Hospital and PLA Medical College, 28 Fu Xing Road, Haidian District, Beijing 100853, China. fuxiaobing@vip.sina.com.
  • 5 Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing 100048, China.
PMID: 33853767 DOI: 10.1126/sciadv.abb2213
Abstract

Intestinal goblet cells secrete mucus layers protecting the intestinal epithelia against injuries. It is challenging to study the interaction of goblet cells, mucus layers, and gut microbiota because of difficulty in producing goblet cells and mucus models. We generate intestinal goblet cells from human epidermal stem cells with two small molecular inhibitors Repsox and CHIR99021 in the presence of basic Fibroblast Growth Factor and bone morphogenetic protein 4 at high efficiency (~95%) of conversion for a short time (6 to 8 days). Induced goblet cells are functional to secrete mucus, deliver fluorescent antigen, and form mucus layers modeling the mucus-microbe interaction in vitro. Transplantation of induced goblet cells and oral administration of chemical induction media promote the repair of the intestinal epithelia in a colitis mouse model. Thus, induced goblet cells can be used for investigating mucus-microbe interaction, and chemical cocktails may act as drugs for repairing the intestinal epithelia.

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