Introduction Heterogeneity within and between cellular populations dictates the fate of all tissues in both normal development and disease pathogenesis. The development of single-cell approaches has revealed amazing diversity across tissues. While the majority of methods to define cellular variation are based on the transcriptomics1,2, ascertaining genomic diversity enables the understanding of the underlying blueprint of cellular heterogeneity. Numerous biological studies have demonstrated that accurate identification of genetic variation in single cells is essential for understanding the role of mutation in normal development and in disease3,4,5. Key to detecting this diversity is the ability to faithfully replicate the genomes that are not detectable reliably at the single cell level without prior amplification. The development of Primary Templatedirected Amplification (Figure 1) for individual cells and low DNA inputs allows for amplification with unprecedented uniformity, providing revolutionary sequencing breadth and sensitivity6.