Man, Jun Cai, Max A Cayo, Sunil K Mallanna and Stephen
Man, Jun Cai, Max A Cayo, Sunil K Mallanna and Stephen A Duncan*AbstractBackground: The 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 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27741243 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. Results: We 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. Conclusions: iPSCs that harbor an abnormal chromosomal content retain the capacity to generate hepatocyte ike cells with high efficiency. Keywords: iPSC, Hepatocyte differentiation, AneuploidyBackground The availability of human pluripotent stem cells has provided a cell culture platform for study of human disease and development [1]. Pluripotent cells could also AG-490MedChemExpress AG-490 potentially be used therapeutically as a source of cells for transplant or drug discovery. Moreover, the finding that patient pecific pluripotent cells can be relatively easily generated by molecular reprogramming raises the prospect of using personalized regenerative medicine to treat a variety of diseases, arguably without fear of immune rejection [2,3]. While the biomedical potential of pluripotent stem cells is irrefutable, to realize such potential requires an in depth understanding of the* Correspondence: [email protected] Equal contributors Department of Cell Biology, Neurobiology and Anatomy, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USAfundamental properties and complications that are associated with genomic changes that accompany the reprogramming process. Many studies have revealed that, as a consequence of reprogramming and stem cell culture, genetic instability commonly occurs [4]. The genetic variations that have been observed are diverse and include copy number variations (CNVs), chromosomal rearrangements, and several sub-chromosomal mutations including deletions and point mutations [5-10]. For pluripotent cells to be used safely in regenerative medicine, substantial characterization would therefore be necessary to ensure the genomic integrity of transplantable cells. Although it is clear that iPSC erived cells used for cell therapy should be euploid due to the need for safety, how chromosomal variation affects the production of differentiated cells in culture remains ill defined. Cell differentiation is an orchestrated process that relies on?2014 Noto et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of.