Abstract
Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function studies reveal that SALL3 inversely regulates the differentiation of hiPSCs into cardiomyocytes and neural cells. Mechanistically, SALL3 modulates DNMT3B function and DNA methyltransferase activity, and influences gene body methylation of Wnt signaling-related genes in hiPSCs. These findings suggest that SALL3 switches the differentiation propensity of hiPSCs toward distinct cell lineages by changing the epigenetic profile and serves as a marker for evaluating the hiPSC differentiation propensity.
Highlights
Clinical applications of human induced pluripotent stem cells are expected, but human-induced pluripotent stem cell (hiPSC) lines vary in their differentiation propensity
Hypothesizing that some critical attribute in hiPSCs underlies the determination of propensity to differentiate into a specific lineage, we attempted to find potential marker genes, the expression of which in hiPSCs significantly correlated with the efficacy of differentiation into three germ layers
To profile differences in the ability to differentiate into the three germ layers, we examined differentiation propensity of ten hiPSC lines via spontaneous differentiation during embryoid body (EB) formation without addition of growth factors to minimize any bias toward differentiation
Summary
Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. Human pluripotent stem cells (hPSCs) have the ability to differentiate into various types of cells and to self-renew in vitro Because of these two characteristics, hPSCs are expected to provide new applications for regenerative medicine/ cell therapy. We identify the SALL3 gene as a marker predictive of differentiation propensity, using the rank correlation method and analysis of ten hiPSC lines. SALL3 is found to repress gene body methylation in hiPSCs, leading to their epigenetic changes These findings provide a practical method for selecting appropriate hPSC lines in clinicalgrade cell banks, allowing the prediction of differentiation capacity toward a desired cell lineage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
