Xiaojun Lance Lian, Assistant Professor | Departments of Biomedical Engineering & Biology, The Pennsylvania State University and Penn State Cancer Institute | Huck Institutes, Center for Molecular Immunology and Infectious Disease
Abstract: Human pluripotent stem cells (hPSCs) offer the potential to generate large numbers of functional cardiomyocytes from clonal and patient-specific cell sources. Here we show that temporal modulation of Wnt signaling is both essential and sufficient for efficient cardiac induction in hPSCs under defined, growth factor-free conditions. shRNA knockdown of β-catenin during the initial stage of hPSC differentiation fully blocked cardiomyocyte specification, whereas glycogen synthase kinase 3 inhibition at this point enhanced cardiomyocyte generation. Furthermore, sequential treatment of hPSCs with glycogen synthase kinase 3 inhibitors followed by inducible expression of β-catenin shRNA or chemical inhibitors of Wnt signaling produced a high yield of virtually (up to 98%) pure functional human cardiomyocytes from multiple hPSC lines. The robust ability to generate functional cardiomyocytes under defined, growth factor-free conditions solely by genetic or chemically mediated manipulation of a single developmental pathway should facilitate scalable production of cardiac cells suitable for research and regenerative applications.
Bio: Dr. Lance Lian received his PhD in Chemical engineering from University of Wisconsin-Madison in 2012. During his PhD, Dr. Lian's “Cardiomyocyte Differentiation from Human Pluripotent Stem Cells” paper was awarded the best biomedical paper in PNAS and the Cozzarelli Prize of the National Academy of Sciences in 2012. Dr. Lian did his postdoc training at Harvard University and Karolinska Institute for stem cell research. After joining Penn State in 2015, Dr. Lian developed the world’s first pancreatic cell differentiation method from stem cells for treating diabetes with only small molecules, which makes this production much more cost-effective and efficient.
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