ATACing single cells with phages.

Area of Science:

• Single-cell biology
• Molecular biology
• Genomics

Background:

• Understanding cellular heterogeneity requires methods to simultaneously analyze multiple molecular layers within individual cells.
• Current single-cell multi-omics techniques face challenges in throughput and the range of analytes that can be measured.

Purpose of the Study:

• To develop a novel multi-omics approach for high-throughput single-cell analysis.
• To integrate phage-displayed single-domain antibodies (nanobodies) with the assay for transposase-accessible chromatin (PHAGE-ATAC).

Main Methods:

• The study combined nanobody-based protein detection with PHAGE-ATAC for chromatin accessibility profiling.
• Mitochondrial DNA mutations were incorporated for clonal tracing within single cells.

Main Results:

• Simultaneous measurement of protein expression, chromatin accessibility, and mitochondrial DNA mutations in single cells was achieved.
• The developed method provides a comprehensive view of cellular states and clonal relationships.

Conclusions:

• This integrated multi-omics strategy offers a powerful tool for dissecting cellular heterogeneity and dynamics.
• The approach has broad applicability in various fields, including developmental biology and cancer research.