From here, the focus of discussions turned toward novel methods to generate defined cell types and their application toward a number of highly penetrant neurodevelopmental and neurodegenerative disorders. There was consistent discussion of the critical need to build complexity into hiPSC-based models of neuronal development, first, by more efficiently differentiating and maturing pure populations of neurons, astrocytes, and other neural cell types, and, second, by allowing these populations to self-organize into defined circuits and three-dimensional (3D) systems (organoids) (Eiraku et al., 2008, Kadoshima et al., 2013, Mariani et al., 2012). Earlier work had shown that organoids recapitulate morphogen gradients, cell polarity, layer formation, and other essential features of morphogenesis. Ultimately, there is a need to return to the in vivo environment, and a number of researchers discussed early work in transplanting human hiPSC neurons back into either fetal or adult mouse brains (chimeras), in order to track connectivity and systems-level functionality of these cells in vivo (Muotri et al., 2005), on the basis of early evidence that hESC-derived human neurons can cross-talk with mouse neurons.
