The transcriptome dynamics of single cells during the cell cycle

Despite advances in single-cell data analysis, the dynamics and topology of the cell cycle in high-dimensional gene expression space remains largely unknown. Here, we use a linear analysis of transcriptome data to reveal that cells move along a circular trajectory in transcriptome space during the cell cycle. This movement occurs largely independently from other cellular processes. Non-cycling gene expression (changes in environment or epigenetic state) adds a third dimension and causes helical motion on a hollow cylinder. The circular trajectory shape indicates minimal acceleration of transcription, i.e. the cell cycle has evolved to minimize changes of transcriptional activity and its entailing regulatory effort. Thus, we uncover a general design principle of the cell cycle that may be of relevance to many other cellular differentiation processes. One Sentence SummaryCells traverse high-dimensional gene expression space in a 2D circular motion, thus minimizing changes of expression changes ("Acceleration").