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An in vitro model of polycystic liver disease using genome-edited human inducible pluripotent stem cells
- Source :
- Stem Cell Research, Vol 32, Iss, Pp 17-24 (2018)
- Publication Year :
- 2017
-
Abstract
- In the developing liver, bile duct structure is formed through differentiation of hepatic progenitor cells (HPC) into cholangiocytes. A subtype of polycystic liver diseases characterized by uncontrolled expansion of bile ductal cells is caused by genetic abnormalities such as in that of protein kinase C substrate 80 K-H (PRKCSH). In this study, we aimed to mimic the disease process in vitro by genome editing of the PRKCSH locus in human inducible pluripotent stem (iPS) cells. A proportion of cultured human iPS cell-derived CD13+CD133+ HPC differentiated into CD13− cells. During the subsequent gel embedding culture, CD13− cells formed bile ductal marker-positive cystic structures with the polarity of epithelial cells. A deletion of PRKCSH gene increased expression of cholangiocytic transcription factors in CD13− cells and the number of cholangiocytic cyst structure. These results suggest that PRKCSH deficiency promotes the differentiation of HPC-derived cholangiocytes, providing a good in vitro model to analyze the molecular mechanisms underlying polycystic diseases. Keywords: Human iPS cells, Polycystic liver disease, Genome editing, Cholangiocyte
- Subjects :
- 0301 basic medicine
Ductal cells
Biology
CD13 Antigens
Cholangiocyte
Cell Line
03 medical and health sciences
medicine
Humans
AC133 Antigen
Progenitor cell
Induced pluripotent stem cell
Gene
Transcription factor
lcsh:QH301-705.5
Cells, Cultured
Gene Editing
PRKCSH
Cysts
Polycystic liver disease
Liver Diseases
Calcium-Binding Proteins
Intracellular Signaling Peptides and Proteins
Cell Differentiation
Cell Biology
General Medicine
medicine.disease
Flow Cytometry
Cell biology
030104 developmental biology
lcsh:Biology (General)
Liver
Glucosidases
Developmental Biology
Subjects
Details
- ISSN :
- 18767753
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Stem cell research
- Accession number :
- edsair.doi.dedup.....fc44ea22212b6c3632148f59ba3aaab5