Towards a Cell Cycle Atlas

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The cell cycle is a fundamental process over which the cell grows and divides. This highly regulated series of events is known to be an important contributor to variations in protein and RNA expression between individual cells. Today we are releasing version 20.1 of the Human Protein Atlas (HPA), adding new data to the Cell Atlas, which allows detailed exploration of protein and RNA expression in relation to cell cycle progression.

The numerous ICC-IF images publicly available in the Cell Atlas of the Human Protein Atlas (HPA), is a great resource to study heterogeneity in the expression, as well as subcellular localization, of proteins in human cells. As many as 25% of the genes represented in the Cell Atlas encode proteins that display variations in protein expression patterns between genetically identical cells. The cell cycle, over which the cell grows and divides, is a known source of differences in both transcript and protein abundances within unsynchronized cell cultures. Therefore, researchers within the HPA set out to determine how much of the observed variations can be attributed to the cell cycle.

In this study, single-cell temporal RNA and protein expression patterns have been further characterized in the Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) U-2 OS cell line. This cell line allows determination of cell cycle progression in individual cells by measuring the relative intensity of two fluorescent markers. Imaging proteogenomics and single-cell RNA sequencing of cells in different phases of the cell cycle has enabled a detailed analysis of protein and RNA abundance in relation to cell cycle progression. This has led to the identification of 529 genes encoding cell cycle dependent proteins, almost half of which have no previously known association to the cell cycle, as well as 401 genes encoding cell cycle dependent transcripts.

The data from this publication has now been integrated into the Cell Atlas, providing a spatially resolved proteomic map of the cell cycle. The detailed plots of single-cell protein and RNA expression levels over the course of the cell cycle provides a new resource for molecular insights into this process and cellular proliferation. Furthermore, the finding that the majority of proteins in this study showed cell-to-cell variations in expression that was largely unexplained by the cell cycle opens up intriguing avenues for further exploration of the stochasticity and/or deterministic factors that govern this phenomenon, as well as a potential role in regulating other cellular states and functions.


Read the publication in Nature

The cell cycle dependent proteome and transcriptome

Ulrika Axelsson