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In the same cell, the proteome defines cellular state and the transcriptome marks transitions

Bulk transcriptome and proteome correlate only modestly, but this has not been investigated in the same cell or across cell-state changes. Here we introduce a scalable technology that quantifies thousands of proteins and transcripts in the same cell, separating RNA from protein by tip-based C18 capture and pairing full-length RNA sequencing with latest-generation mass spectrometry. In HeLa cells,…

A new technology has been developed that can measure thousands of proteins and transcripts within a single cell simultaneously. In HeLa cells, the abundances of RNA and protein match up well within each cell, with an r value of 0.45. However, the two do not correlate across the population of cells, with an r value of 0.038. During the process of pluripotency transitions, only one-third of matched transcripts and proteins change in sync, yet the transcription factors that define each state remain tightly regulated.

The amount of variance in transcripts is several-fold greater than the variance in proteins, which reflects the phenomenon of transcriptional bursting and mRNA sampling noise. As a result, the proteome serves as the stable, low-noise definition of cell state, while the transcriptome marks cellular transitions. Consequently, the proteome can define cell state using far fewer cells.

Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.

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