A single-cell massively parallel reporter assay detects cell type specific cis-regulatory activity
A single-cell massively parallel reporter assay detects cell type specific cis-regulatory activity
Massively parallel reporter gene assays are key tools in regulatory genomics, but cannot be used to identify cell-type specific regulatory elements without performing assays serially across different cell types. To address this problem, 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. 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 that detects cell-type specific cis-regulatory activity. We then measured a library of promoter variants across multiple cell types in ex vivo mouse retinas and showed that subtle genetic variants can produce cell-type specific effects on cis-regulatory activity. We anticipate that scMPRA will be widely applicable for studying the role of CRSs across diverse cell types.
Zhao Siqi、White Michael A、Myers Connie A、Cohen Barak A、Hong Clarice KY、Granas David M、Corbo Joseph C
Edison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine||Department of Genetics, Washington University School of MedicineEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine||Department of Genetics, Washington University School of MedicineDepartment of Pathology, Washington University School of MedicineEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine||Department of Genetics, Washington University School of MedicineEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine||Department of Genetics, Washington University School of MedicineEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine||Department of Genetics, Washington University School of MedicineDepartment of Pathology, Washington University School of Medicine
生物科学研究方法、生物科学研究技术分子生物学遗传学
Zhao Siqi,White Michael A,Myers Connie A,Cohen Barak A,Hong Clarice KY,Granas David M,Corbo Joseph C.A single-cell massively parallel reporter assay detects cell type specific cis-regulatory activity[EB/OL].(2025-03-28)[2025-05-26].https://www.biorxiv.org/content/10.1101/2021.11.11.468308.点此复制
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