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A reference atlas of human cell types is a major goal for the field. Here, we set out to generate single-cell atlases of both gene expression (this study) and chromatin accessibility (Domcke et al., this issue) using diverse human tissues obtained during midgestation.

Contemporary knowledge of the molecular basis of in vivo human development mostly derives from a combination of human genetics, in vivo investigations of model organisms, and in vitro studies of differentiating human cell lines, rather than through direct investigations of developing human tissues. Several challenges have historically limited the study of developing human tissues at the molecular level, including limited access, tissue degradation, and cell type heterogeneity. For this and the companion study (Domcke et al., this issue), we were able to overcome these challenges.

We applied three-level single …