In this issue of Genome Biology, Tsang and colleagues utilize the Fluidigm C1 microfluidic system to profile a total of 180 hematopoietic stem cells (HSCs) from mice of two different genetic backgrounds using single-cell RNA-sequencing (scRNA-seq). They leverage these data to interrogate the primary sources of expression variability in HSCs, and to better understand how cellular heterogeneity is affected by the deletion of Bcl11a. Their findings highlight multiple roles for this important regulator, and point to the power of single-cell transcriptomics for disentangling heterogeneous and developing systems.