Stem Cell Foundation

This week, we report in @Nature our effort to identify molecular convergence and divergence in #autism spectrum disorder (ASD) using human stem cell models. In this collaborative study with Dan Geschwind's lab, spanning almost a decade, we derived 96 hiPS cell lines representing 8 genetic forms of ASD, idiopathic patients, and 20 controls, and after rigorous quality control differentiated 70 lines in more than 150 experiments into human cortical #organoids for 100 days. Interestingly, early time points harbored the largest mutation-specific changes, but distinct mutations converged on shared transcriptional changes as development progressed. This is just the beginning: we will need larger cohorts and more advanced cultures that capture cell diversity and interactions, such as #assembloids. Still, this initial study illustrates how risk associated with genetically defined forms of ASD can propagate through transcriptional regulation, leading to convergent and divergent signaling defects. This work was spearheaded by the heroic efforts of Aaron Gordon and Se-Jin Yoon, together with Lucy Bicks!