PT - JOURNAL ARTICLE AU - Peng Hu AU - Emily Fabyanic AU - Zhaolan Zhou AU - Hao Wu TI - sNucDrop-Seq: Dissecting cell-type composition and neuronal activity state in mammalian brains by massively parallel single-nucleus RNA-Seq AID - 10.1101/154476 DP - 2017 Jan 01 TA - bioRxiv PG - 154476 4099 - http://biorxiv.org/content/early/2017/07/02/154476.short 4100 - http://biorxiv.org/content/early/2017/07/02/154476.full AB - Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues, such as adult mammalian brains, is challenging. Here, we integrate sucrose-gradient assisted nuclear purification with droplet microfluidics to develop a highly scalable single-nucleus RNA-Seq approach (sNucDrop-Seq), which is free of enzymatic dissociation and nucleus sorting. By profiling ∼11,000 nuclei isolated from adult mouse cerebral cortex, we demonstrate that sNucDrop-Seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity, but also enables analysis of long non-coding RNAs and transient states such as neuronal activity-dependent transcription at single-cell resolution in vivo.