Generation of high quality of hepatocyte-like cells from induced pluripotent stem cells with Parp1 but lacking c-Myc

J Chin Med Assoc. 2018 Oct;81(10):871-877. doi: 10.1016/j.jcma.2018.06.002. Epub 2018 Jul 13.

Abstract

Background: Induced pluripotent stem cells (iPSCs) have a great potential for application in patient-specific therapy. The reprogramming method that does not involve c-Myc reduces tumorigenic risk, but also largely reduces the efficiency of generation of iPSCs, especially for those reprogrammed from damaged cells. Poly(ADP-ribose) polymerase 1 (Parp1) catalyzes a reaction of poly(ADP-ribosylation) and has been reported to enhance cell reprogramming.

Methods: Using Oct-4/Sox2/Klf4/Parp1 (OSKP) reprogramming method, reprogramming factors plus Parp1 were capable of generation of iPSCs from adult fibroblasts and further toward to differentiate from iPSCs status into hepatocyte-like cells.

Results: Our results showed that Oct-4/Sox2/Klf4/Parp1 (OSKP)-derived iPSC exhibited regular pluripotent properties, long-term passages and more stable cellular-divided period. These OSKP-derived iPSCs can effectively differentiate into hepatocyte-like cells (OSKP-iPSC-Heps), and present high mRNA levels of Sox17, HNF3b, and HNF4a in OSKP-iPSC-Heps. The mature hepatic functions, including CYP3A4, LDL uptake, glycogen synthesis and urea secretion were analyzed and well detected in OSKP-iPSC-Heps on day 14 post-differentiation.

Conclusion: In conclusion, we demonstrated that Parp1 promoted reprogramming process to generate the high quality of iPSCs, which could be used as a high quality source of hepatocytes.

Keywords: Hepatocyte; Induced pluripotent stem cells; Poly(ADP-ribose) polymerase 1.

MeSH terms

  • Cell Differentiation
  • Cellular Reprogramming / physiology*
  • Hepatocytes / cytology*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / physiology
  • Octamer Transcription Factor-3 / physiology
  • Poly (ADP-Ribose) Polymerase-1 / physiology*
  • Proto-Oncogene Proteins c-myc / physiology*
  • SOXB1 Transcription Factors / physiology

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Poly (ADP-Ribose) Polymerase-1