Time-lapse single-cell transcriptomics reveals modulation of histone H3 for dormancy breaking

How quiescent cells break dormancy is a key issue in eukaryotic cells including cancer. Fungal spores, for example, remain quiescent for long periods until nourished, although the mechanisms by which dormancy is broken remain enigmatic. Transcriptome analysis could provide a clue, but methods to synchronously germinate large numbers of spores are lacking, and thus it remains a challenge to analyse gene expression upon germination. Hence, we developed methods to assemble transcriptomes from individual, asynchronous spore cells of fission yeast undergoing germination to assess transcriptomic changes over time. The virtual time-lapse analyses highlighted one of three copies of histone H3 genes for which transcription fluctuates during the initial stage of germination. Disruption of this temporal fluctuation caused defects in spore germination despite no visible defects in other stages of the life cycle. We conclude that modulation of histone H3 expression is a crucial ‘wake-up’ trigger at dormancy breaking.