2. Academic Validation
  3. IFI16 promotes human embryonic stem cell trilineage specification through interaction with p53

IFI16 promotes human embryonic stem cell trilineage specification through interaction with p53

  • NPJ Regen Med. 2020 Oct 29;5(1):18. doi: 10.1038/s41536-020-00104-0.
Qian He 1 2 3 4,  Zubiao Wu 1 3 4,  Wei Yang 1 3 4,  Doukou Jiang 1 3 4,  Chaofeng Hu 2,  Xiaofei Yang 5 6 7 8,  Ning Li 9 10 11 12,  Furong Li 13 14 15 16
Affiliations

Affiliations

  • 1 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China.
  • 2 Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, 510632, Guangzhou, China.
  • 3 Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China.
  • 4 Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China.
  • 5 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China. sophiayangxf@163.com.
  • 6 Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. sophiayangxf@163.com.
  • 7 Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. sophiayangxf@163.com.
  • 8 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. sophiayangxf@163.com.
  • 9 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China. lining.yatu@hotmail.com.
  • 10 Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. lining.yatu@hotmail.com.
  • 11 Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. lining.yatu@hotmail.com.
  • 12 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. lining.yatu@hotmail.com.
  • 13 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China. frli62@163.com.
  • 14 Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. frli62@163.com.
  • 15 Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. frli62@163.com.
  • 16 Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. frli62@163.com.
PMID: 33298947 DOI: 10.1038/s41536-020-00104-0
Abstract

Transcriptional regulation plays an essential role in the self-renewal and differentiation of human embryonic stem cells (hESCs). However, how external signals disrupt the self-renewal regulatory network and further drive hESC differentiation remains largely unknown. Here, we found the immune regulative protein, gamma-interferon-inducible protein 16 (IFI16) was involved in the regulation of both self-renewal and differentiation gene expression during hESC trilineage specification through interaction with p53. IFI16 expression levels were upregulated through JNK activation. IFI16 knockdown delayed the downregulation of self-renewal gene expression and suppressed the upregulation of differentiation gene expression, while IFI16 overexpression accelerated trilineage specification. Furthermore, IFI16 stabilized p53-binding in the genome through IFI16-p53 interaction and differentially regulated self-renewal and differentiation gene expression. Together, our results suggest a particular role of IFI16 in differential gene expression regulation during trilineage specification of hESCs in a manner that is dependent on the genome-wide profile of p53-binding directed by IFI16-p53 interaction.

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