Phospho-seq: integrated, multi-modal profiling of intracellular protein dynamics in single cells

Research Overview

Cell signaling steers neurodevelopment, but profiling signaling states alongside other molecular layers at single-cell scale has remained hard to do flexibly. Phospho-seq is an integrated approach that quantifies cytoplasmic and nuclear proteins — including post-translationally modified forms — and connects their activity to cis-regulatory elements and transcriptional targets.

A simplified benchtop antibody-conjugation method enabled large custom neuro-focused antibody panels for simultaneous protein and single-cell ATAC-seq profiling on whole cells, with experimental and computational strategies to fold in transcriptomic measurements. The workflow was applied to cell lines, induced pluripotent stem cells, and months-old brain organoids.