GUEST SPEAKER: Dr Kouichi Hasegawa
Senior Lecturer, Institute for Integrated Cell-Material Science (iCeMS), Kyoto University, Japan
Assistant Professor, Institute for Stem Cell Biology and Regenerative Medicine (inStem), National Centre for Biological Sciences, India
Title: Wnt-dependent and FGF/TGFβ-independent Human Pluripotent Stem Cell Renewal
Decision of self-renewal or differentiation in stem cells in vitro culture and in vivo is controlled by extrinsic factors such as signaling molecules. The extrinsic factors regulating human pluripotent stem cell (iPS cells or ES cells) self-renewal and early differentiation events seem to differ from mouse pluripotent stem cell and to date are incompletely understood, but activation of bFGF and TGFβ/activin/Nodal signaling form the cornerstone of most systems for human ES cell propagation. The Wnt/β-catenin signaling pathway plays an important role in mouse ES cell self-renewal in LIF-independent culture but it is dispensable in LIF-dependent culture. In human pluripotent stem cells, the role of Wnt/β-catenin signaling is still poorly understood and controversial because of the dichotomous behavior of Wnt/β-catenin signaling in proliferation and differentiation.
While investigating small molecule chemical compounds that could segregate the dual role of Wnt signaling, we have identified a compound that could modulate Wnt/β-catenin signaling pathway and support Wnt-induced human ES cell self-renewal without affecting differentiation. Utilizing Wnt and the compound, we have developed a novel and simple chemically defined xeno-free culture system that allows for long-term expansion of human pluripotent stem cells without FGF or TGFβ supplementation. These culture conditions do not include xenobiotic supplements, serum, serum replacement or albumin. Using this culture system, we have shown that several human pluripotent cell lines maintained pluripotency (>20 passages) and a normal karyotype, and still retained the ability to differentiate into derivatives of all three germ layers. This Wnt-dependent and bFGF/TGFβ-independent culture system would provide a platform for complete replacement of growth factors with chemical compounds.
VENUE: Melbourne Brain Centre, The University of Melbourne