Single cell transcriptome analysis of the effect of the 16p11.2 microdeletion on hIPSC derived developing human GABAergic neurons

The 16p11.2 microdeletion is one of the most common genetic risk factors for autism spectrum condition. In this study we test the hypothesis that the 16p11.2 microdeletion impacts the development of GABAergic neurons by affecting gene transcription during their development. We employed a culture protocol reported to direct human induced pluripotent stem cells (hIPSCs) along a forebrain GABAergic neuron trajectory (Liu et al., 2013) using hIPSC lines engineered to harbour the 16p11.2 microdeletion and isogenic controls (Tai at al., 2016). After 80 days in culture three cultures of each genotype were subjected to library preparation and 10x single cell sequencing to generate 33954 single cell transcriptomes (~5000/culture).References:Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC. (2013) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc. 8:1670-9. doi: 10.1038/nprot.2013.106. Tai DJ, Ragavendran A, Manavalan P, Stortchevoi A, Seabra CM, Erdin S, Collins RL, Blumenthal I, Chen X, Shen Y, Sahin M, Zhang C, Lee C, Gusella JF, Talkowski ME. (2016) Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. Nat Neurosci. 19:517-22. doi: 10.1038/nn.4235.