T-47D Giredestrant + palbociclib combination TraCe-seq (NGS4327)

Barcoded clones of T-47D cells were treated with either giredestrant, palbociclib, or their combination for different duration. Barcodes and transcriptional profiles was measured by scRNA-seq. Overall design: T-47D cell lines were barcoded with TraCe-seq barcoding libraries and expanded in culture to establish the starting TraCe-seq cell populations. A fraction of the starting populations were profiled by single cell RNA-sequencing (scRNA-seq) to capture the relative clonal abundance and transcriptional profile of each barcoded clones right before drug treatment. In parallel, the rest of the cells were treated with giredestrant or palbociclib alone or in combination until resistant clones emerged. We conducted scRNA-seq profiling to capture acute responses to the treatment at 1, 4, 8, and 26 days post treatment as well as after 6 months for the combination treamtent to capture adaptive changes. These time points were chosen to allow us capture the differential transcriptional responses in the resistant versus sensitive clones, and compare the responses to the different treatments at individual clone and single cell level.