Targeted Chromatin Profiling in Muscle Stem Cells Using a CUT&RUN-qPCR Strategy

Chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR), even after extensive optimization, is often limited by low signal-to-background ratio, particularly when cell numbers are restricted. This represents a major challenge for muscle stem cells (MuSCs), a rare population that cannot be obtained in large quantities. To overcome these limitations, we adapted Cleavage Under Targets and Release Using Nuclease (CUT&RUN) into a targeted CUT&RUN-qPCR strategy. This approach enables sensitive analysis of chromatin-protein interactions at defined loci from low-input samples, without the need for genome-wide sequencing. Using limited numbers of cells (150,000 MuSCs), we provide a robust and scalable solution for targeted chromatin profiling in rare stem cell populations.