Abstract

Fission yeast, Schizoaccharomyces pombe, is a model for studying cellular quiescence. Shifting to a medium that lacks a nitrogen-source induces proliferative cells to enter long-term G0 quiescence. Klf1 is a Krüppel-like transcription factor with a 7-amino acid Cys2His2-type zinc finger motif. The deletion mutant, ∆klf1, normally divides in vegetative medium, but proliferation is not restored after long-term G0 quiescence. Cell biologic, transcriptomic, and metabolomic analyses revealed a unique phenotype of the ∆klf1 mutant in quiescence. Mutant cells had diminished transcripts related to signaling molecules for switching to differentiation; however, proliferative metabolites for cell-wall assembly and antioxidants had significantly increased. Further, the size of ∆klf1 cells increased markedly during quiescence due to the aberrant accumulation of Calcofluor-positive, chitin-like materials beneath the cell wall. After 4 weeks of quiescence, reversible proliferation ability was lost, but metabolism was maintained. Klf1 thus plays a role in G0 phase longevity by enhancing the differentiation signal and suppressing metabolism for growth. If Klf1 is lost, S. pombe fails to maintain a constant cell size and normal cell morphology during quiescence.

Highlights

  • All cells exist in one of two states, proliferative and quiescent

  • The Klf1 protein was tagged with green fluorescence protein (GFP) at the carboxy-terminus, encoded by the fusion gene chromosomally integrated at the native klf1 locus, and expressed under the native promoter (Materials and Methods)

  • Comparison with the 4',6-diamidino-2phenylindole (DAPI) staining pattern revealed that KLF1-GFP accumulated in the nucleolar region [31,32] and not in the chromatin region in vegetative cells

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Summary

Introduction

All cells exist in one of two states, proliferative and quiescent. The cell number increases by division, while in the quiescent state, cell life is sustained without division [1,2,3,4,5,6,7]. The majority of cells in tissues and organs are non-dividing, so quiescence is a common cell state. In the body of a complex organism, some cell types continuously transition between proliferative and quiescent. Hematopoietic stem cells give rise to all blood cells during an individual’s lifetime; their proliferation and quiescence are carefully regulated [8,9]. The cellular mechanism for the transition between proliferation and quiescence is intriguing

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