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In recent years, the single-cell genomics field has made incredible progress toward disentangling the cellular heterogeneity of human tissues. However, the overwhelming majority of effort has been focused on single-cell gene expression rather than the chromatin landscape that shapes and is shaped by gene expression. Toward advancing our understanding of the regulatory programs that underlie human cell types, we set out to generate single-cell atlases of both chromatin accessibility (this study) and gene expression (Cao et al., this issue) from a broad range of human fetal tissues.

Regions of accessible chromatin in our genome, such as enhancers, play key roles in the determination and maintenance of cell fates. Accessible regions are also markedly enriched for genetic variation that contributes to common disease heritability. The vast majority of chromatin accessibility data …