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
  • 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. [email protected].
  • 6. Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. [email protected].
  • 7. Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. [email protected].
  • 8. Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. [email protected].
  • 9. Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China. [email protected].
  • 10. Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. [email protected].
  • 11. Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. [email protected].
  • 12. Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. [email protected].
  • 13. Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 518020, Shenzhen, China. [email protected].
  • 14. Guangdong Engineering Technology Research Center of Stem Cell and Cell therapy, 518020, Shenzhen, China. [email protected].
  • 15. Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, 518020, Shenzhen, China. [email protected].
  • 16. Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 1017 Dongmen North Road, 518020, Shenzhen, China. [email protected].
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.

Products