Abstract
BackgroundThe characterization of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) routinely includes analyses of chromosomal integrity. The belief is that pluripotent stem cells best suited to the generation of differentiated derivatives should display a euploid karyotype; although, this does not appear to have been formally tested. While aneuploidy is commonly associated with cell transformation, several types of somatic cells, including hepatocytes, are frequently aneuploid and variation in chromosomal content does not contribute to a transformed phenotype. This insight has led to the proposal that dynamic changes in the chromosomal environment may be important to establish genetic diversity within the hepatocyte population and such diversity may facilitate an adaptive response by the liver to various insults. Such a positive contribution of aneuploidy to liver function raises the possibility that, in contrast to existing dogma, aneuploid iPSCs may be capable of generating hepatocyte-like cells that display hepatic activities.ResultsWe examined whether a human iPSC line that had multiple chromosomal aberrations was competent to differentiate into hepatocytes and found that loss of normal chromosomal content had little impact on the production of hepatocyte-like cells from iPSCs.ConclusionsiPSCs that harbor an abnormal chromosomal content retain the capacity to generate hepatocyte–like cells with high efficiency.
Highlights
The characterization of induced pluripotent stem cells and embryonic stem cells (ESCs) routinely includes analyses of chromosomal integrity
Characterization of aneuploid Induced pluripotent stem cell (iPSC) We have previously described the generation of a human iPSC line, referred to as iPSC-K3, which was produced by reprogramming foreskin fibroblasts using transient transfection of plasmids that express OCT4, NANOG, LIN28, and KLF4 [13]
These iPSCs are free of integrated exogenous DNA and have a high capacity to differentiate into cells that display characteristics of hepatocytes
Summary
The characterization of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) routinely includes analyses of chromosomal integrity. While aneuploidy is commonly associated with cell transformation, several types of somatic cells, including hepatocytes, are frequently aneuploid and variation in chromosomal content does not contribute to a transformed phenotype This insight has led to the proposal that dynamic changes in the chromosomal environment may be important to establish genetic diversity within the hepatocyte population and such diversity may facilitate an adaptive response by the liver to various insults. Such a positive contribution of aneuploidy to liver function raises the possibility that, in contrast to existing dogma, aneuploid iPSCs may be capable of generating hepatocyte-like cells that display hepatic activities. For pluripotent cells to be used safely in regenerative medicine, substantial characterization would be necessary to ensure the genomic integrity of transplantable cells
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