<p>Single-cell profiling protein-chromatin interactions is often constrained by complex workflows, high cost, or dependence on specialized equipment. We present indexed tagmentation-based single-cell CUT&amp;Tag-sequencing (IT-scC&amp;T-seq), a modular, plate-based strategy using three-round combinatorial barcoding. IT-scC&amp;T-seq robustly profiles histone modifications and transcription factors with high specificity and throughput, supporting simultaneous analysis of multiple samples and epitopes. Notably, it enables sensitive single-cell mapping of lamina-associated domains, low-abundance chromatin features previously difficult to resolve. Applied to adult mouse mammary gland, the method reveals cell-type-specific chromatin landscapes and lineage-regulatory dynamics. Together, IT-scC&amp;T-seq provides a scalable, cost-effective, and broadly accessible approach for high-resolution chromatin profiling.</p>

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IT-scC&T-seq streamlines scalable, parallel profiling of protein–DNA interactions in single cells

  • Jingchun Ma,
  • Wei Jin,
  • Li Rong,
  • Zhanyu Gao,
  • Zaman Hazrat,
  • Hosen Md Shakhawat,
  • Fei Long,
  • Zixuan Zhang,
  • Jiandong Huang,
  • Xiaomei Lu,
  • Guoxiang Jin,
  • Zhongjun Zhou

摘要

Single-cell profiling protein-chromatin interactions is often constrained by complex workflows, high cost, or dependence on specialized equipment. We present indexed tagmentation-based single-cell CUT&Tag-sequencing (IT-scC&T-seq), a modular, plate-based strategy using three-round combinatorial barcoding. IT-scC&T-seq robustly profiles histone modifications and transcription factors with high specificity and throughput, supporting simultaneous analysis of multiple samples and epitopes. Notably, it enables sensitive single-cell mapping of lamina-associated domains, low-abundance chromatin features previously difficult to resolve. Applied to adult mouse mammary gland, the method reveals cell-type-specific chromatin landscapes and lineage-regulatory dynamics. Together, IT-scC&T-seq provides a scalable, cost-effective, and broadly accessible approach for high-resolution chromatin profiling.