Date(s) - 02/03/2020
3:00 pm - 4:00 pm
The therapeutic application of human induced pluripotent stem cells (hiPSCs) for cartilage regeneration is largely hindered by the low-yield of chondrocytes accompanied by unpredictable and heterogeneous off-target differentiation of cells during chondrogenesis. We combined bulk RNA-seq, scRNA-seq, and bioinformatic analyses, including weighted gene co-expression analysis (WGCNA), to investigate the gene regulatory networks. We identified specific hub genes governing the generation of off-target differentiation into neural cells and melanocytes during hiPSC chondrogenesis. With heterocellular signaling models, we further showed that WNT signaling produced by off-target cells were responsible for inducing chondrocyte hypertrophy. By targeting these hub genes, we eliminated these cell lineages, significantly enhancing the yield and homogeneity of hiPSC-derived chondrocytes. Collectively, our findings identified the trajectories and molecular mechanisms governing cell fate decision in hiPSC chondrogenesis, as well as dynamic transcriptome profiles orchestrating chondrocyte proliferation and differentiation.
Dr. Chia-Lung Wu earned his bachelor’s and Master’s degree in Material Science and Engineering from National Taipei University of Technology and National Taiwan University, respectively. He completed his doctoral training in Biomedical Engineering at Duke University in 2015. Dr. Wu is currently a K99/R00 post-doctoral research associate in Dr. Farshid Guilak’s lab in Orthopedic Surgery at Washington University in Saint Louis. Dr. Wu’s research focuses on identifying the molecular mechanisms by which genetic and epigenetic regulators modulate development, homeostasis and disease progression of musculoskeletal tissues, with a particular focus on cartilage and bone. His approach utilizes bioengineering, cellular biology, next-generation sequencing techniques and genome editing tools, complemented by animal and biomechanical models to uncover these fundamental principles. The long-term goal of his research program is to apply this knowledge to improve tissue engineering outcomes, regeneration and repair for musculoskeletal disorders.