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A single-cell massively parallel reporter assay detects cell type specific cis-regulatory activity

ABSTRACT: We developed a single-cell massively parallel reporter assay (scMPRA) to measure the activity of libraries of cis-regulatory sequences (CRSs) across multiple cell-types simultaneously. As a proof of concept, we assayed a library of core promoters in a mixture of HEK293 and K562 cells and showed that scMPRA is a reproducible, highly parallel, single-cell reporter gene assay. Our results show that housekeeping promoters and CpG island promoters have lower activity in K562 cells relative to HEK293, which likely reflects developmental differences between the cell lines. Within K562 cells, scMPRA identified a subset of developmental promoters that are upregulated in the CD34+/CD38- sub-state, confirming this state as more “stem-like.” Finally, we deconvolved the intrinsic and extrinsic components of cell-to-cell variability and found that developmental promoters have a higher proportion of extrinsic noise compared to housekeeping promoters. We anticipate scMPRA will be widely applicable for studying the role of CRSs across diverse cell types.

ORGANISM(S): Escherichia coli Mus musculus Homo sapiens

PROVIDER: GSE188639 | GEO | 2021/11/11

REPOSITORIES: GEO

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