Altogether, we illustrate the dynamic nature of transcriptional plasticity in propagating clones, highlighting their ability to evolve, adapt, and mature into dominant clones that constitute the majority of tumor cells in secondary xenografts, all originating from a single barcoded cell.

Dominant propagating clones display dynamic transcriptional plasticity which we illustrate by profiling gene expression across generations of cells derived from single starting cells.

Dichotomous cell populations in basal breast cancer distinguish between functional clone types based on differential signaling and metabolic responses. This suggests it is possible to enrich for cells with propagating activity.

In vivo clone doubling time, a metric used to quantify the rate of clonal growth, reveals breast cancer subtype-specific differences in clonal fitness.

We show that extremely rare cells can give rise to clones with propagating activity (frequency 1 in 15,000 – 1 in 116,000). Dominant propagating clones regenerate the full model-specific transcriptional landscape and there is a conserved differentiation program.

In this paper we used expressed lentiviral barcoding to track the clonal growth of over 20,000 single-cell-derived clones in 110 xenografts from 26 patient-derived breast cancer xenograft models. We also profiled 167,375 single-cell RNA profiles to link clonal growth with gene expression.