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PLoS One. 2018 May 11;13(5):e0197046. doi: 10.1371/journal.pone.0197046. eCollection 2018.

Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells.

Author information

1
KU Leuven, Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, Leuven, Belgium.
2
University of Groningen, University Medical Center Groningen (UMCG), Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, Groningen, The Netherlands.
3
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Kerala, India.
4
KU Leuven, Department of Clinical and Experimental Medicine, Clinical and Experimental Endocrinology unit, Leuven, Belgium.
5
University of Groningen, University Medical Center Groningen (UMCG), Department of Obstetrics and Gynecology, Groningen, The Netherlands.

Abstract

Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14 transcription factors (TFs) in reprogramming MAPCs to induced endodermal progenitor cells (iENDO cells), defined as cells that can be long-term expanded and differentiated to both hepatocyte- and endocrine pancreatic-like cells. We demonstrated that 14 TF-iENDO cells can be expanded for at least 20 passages, differentiate spontaneously to hepatocyte-, endocrine pancreatic-, gut tube-like cells as well as endodermal tumor formation when grafted in immunodeficient mice. Furthermore, iENDO cells can be differentiated in vitro into hepatocyte- and endocrine pancreatic-like cells. However, the pluripotency TF OCT4, which is not silenced in iENDO cells, may contribute to the incomplete differentiation to mature cells in vitro and to endodermal tumor formation in vivo. Nevertheless, the studies presented here provide evidence that reprogramming of adult stem cells to an endodermal intermediate progenitor, which can be expanded and differentiate to multiple endodermal cell types, might be a valid alternative for the use of PSCs for creation of endodermal cell types.

PMID:
29750821
PMCID:
PMC5947914
DOI:
10.1371/journal.pone.0197046
[Indexed for MEDLINE]
Free PMC Article

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