Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells

Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12538-43. doi: 10.1073/pnas.1209979109. Epub 2012 Jul 16.


Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many hiPSC clones from adult dermal fibroblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal fibroblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Differentiation*
  • Cells, Cultured
  • Dermis* / cytology
  • Dermis* / metabolism
  • Female
  • Fibroblasts* / cytology
  • Fibroblasts* / metabolism
  • Hep G2 Cells
  • Hepatocytes* / cytology
  • Hepatocytes* / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Male

Associated data

  • GEO/GSE38155