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Single-cell nascent transcription is sparse and heterogeneous, revealing cellular plasticity [pro-seq]

ABSTRACT: Understanding how the genome orchestrates cell diversity requires transcriptional analysis at single-cell resolution. Here, we introduce scFLUENT-seq, a single-cell nascent RNA sequencing technique that detects genome-wide transcription following brief metabolic labeling. Within a 10-minute window, cells from splenic lymphocytes to pluripotent stem cells engage only 0.4~10% of the genome in transcription, compared to >80% in bulk, revealing profound cell-to-cell heterogeneity. Intergenic transcription, especially from heterochromatin, is highly stochastic and pervasive. Promoter-associated antisense and genic transcription rarely co-occur in the same cell. Proximal intergenic transcription reflects both gene readthrough and independent initiation, while distal intergenic transcription is largely decoupled from neighboring gene activity and correlate with greater transcriptional diversity, a hallmark of cellular plasticity. Additionally, mRNA synthesis and decay are poorly coordinated in single cells, suggesting buffering mechanisms that constrain transcriptional noise. Overall, scFLUENT-seq captures both coding and noncoding transcriptional dynamics, revealing the regulatory complexity underlying single-cell heterogeneity and state transitions.

ORGANISM(S): Mus musculus

PROVIDER: GSE278776 | GEO | 2024/10/09

REPOSITORIES: GEO

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Single-cell nascent transcription is sparse and heterogeneous, revealing cellular plasticity [single_cell]

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