Factors from human embryonic stem cell-derived fibroblast-like cells promote topology-dependent hepatic differentiation in primate embryonic and induced pluripotent stem cells.
J Biol Chem, 2010/10/22;285(43):33510-33519.
Huang HP[1], Yu CY[2], Chen HF[3], Chen PH[1], Chuang CY[4], Lin SJ[5], Huang ST[6], Chan WH[7], Ueng TH[8], Ho HN[3], Kuo HC[9]
Affiliations
PMID: 20720011DOI: 10.1074/jbc.M110.122093
Impact factor: 5.486
Abstract
The future clinical use of embryonic stem cell (ESC)-based hepatocyte replacement therapy depends on the development of an efficient procedure for differentiation of hepatocytes from ESCs. Here we report that a high density of human ESC-derived fibroblast-like cells (hESdFs) supported the efficient generation of hepatocyte-like cells with functional and mature hepatic phenotypes from primate ESCs and human induced pluripotent stem cells. Molecular and immunocytochemistry analyses revealed that hESdFs caused a rapid loss of pluripotency and induced a sequential endoderm-to-hepatocyte differentiation in the central area of ESC colonies. Knockdown experiments demonstrated that pluripotent stem cells were directed toward endodermal and hepatic lineages by FGF2 and activin A secreted from hESdFs. Furthermore, we found that the central region of ESC colonies was essential for the hepatic endoderm-specific differentiation, because its removal caused a complete disruption of endodermal differentiation. In conclusion, we describe a novel in vitro differentiation model and show that hESdF-secreted factors act in concert with regional features of ESC colonies to induce robust hepatic endoderm differentiation in primate pluripotent stem cells.
MeSH terms
Activins; Animals; Cell Differentiation; Embryonic Stem Cells; Fibroblast Growth Factor 2; Fibroblasts; Haplorhini; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Liver; Mice
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