Droplet-based proteomics reveals CD36 as a marker for progenitors in mammary basal epithelium

Deep proteomic profiling of rare cell populations has been constrained by sample input requirements. Here, we present DROPPS (droplet-based one-pot preparation for proteomic samples), an accessible low-input platform that generates high-fidelity proteomic profiles of 100–2,500 cells. By applying DROPPS within the mammary epithelium, we elucidated the connection between mitochondrial activity and clonogenicity, identifying CD36 as a marker of progenitor capacity in the basal cell compartment. We anticipate that DROPPS will accelerate biology-driven proteomic research for a multitude of rare cell populations. [Display omitted] •An accessible low-input proteomic method for rare populations of cells•Easy to implement, relying exclusively on common laboratory equipment•Performance is robust across operators and sample processing batches•Identifies CD36 as marker for mammary basal epithelial cells with progenitor capacity Proteomics allows for direct measurement of cellular machinery, allowing for interrogation of a variety of biological systems. Many low-input proteomic methods only support specific study designs or require specialized equipment. To address this limitation, we have developed an accessible low-input proteomic method for studying rare populations of cells: droplet-based one-pot preparation for proteomic samples (DROPPS). Waas et al. develop and validate DROPPS, a proteomic workflow designed to democratize the capacity to profile rare cell populations without compromising data quality. DROPPS generates high-fidelity proteomic profiles from samples comprising as low as 100 cells and is amenable to facile integration with cell sorting.