When our cells sleep: quiescence and renaissance

Living cells are capable of exiting the normal cell cycle (proliferating state) and entering an alternative (sleeping) state termed quiescence. Cells enter into quiescence when they are starved for one or several nutrients. During this fascinating state, they have the intriguing ability to maintain viability for long period (sometimes several months or years) and to resume growth following restoration of the missing nutrient.

Although, in the wild, cells spend most of their time in such a quiescent state, most of the studies performed in research laboratories focus on cells undergoing normal cell cycle. Thus, very little is known about how cells enter into quiescence, how cells survive the lack of nutrients during such long periods, and how they can re-enter the normal cell cycle when the missing nutrient is added.

Quiescent cells have a number of distinguishing characteristics, including a thickened cell wall, specific transcriptional profile, enhanced resistance to heat and oxidative stress… The Taddei team is studying how the chromosomes (support of the genetic information) are organized within the 3-dimensionnal space of the nucleus and how this organization influences their function. We have recently shown that during quiescence, the genome of long-lived quiescent cells undergoes a major spatial re-organization. During exponential phase, the 32 extremities of the yeast chromosomes, named “telomeres” are mainly found at the border of the nucleus and are grouped together forming 3 to 5 foci; in quiescence, telomeres relocalize to the center of the nucleus in a unique “hypercluster”. In addition, super resolution microscopy, allowing the observation of the detailed chromatin structure, reveals that around the telomere hypercluster, the rest of the genome is highly compacted and exhibit a very concentric organization, extremely different from what is observed during the normal cells cycle. Very interestingly, this organization is reversible : the addition of the missing nutrient leads to the disappearance of the telomere hypercluster in less than 30 minutes. The origin and the mechanism of such a dramatic reorganization of the genome is still unknown.

More generally, the mechanisms behind the “quiescence” and “renaissance” of cells remains mysterious and is the focus of many active researches.

References:

Spatial reorganization of telomeres in long-lived quiescent cells

Guidi, M., Ruault, M., Mrbouty, M., Loiodice, I., Cournac. A., Billaudeau, C., Hocher, A., Mozziconacci, J., Koszul, R. Taddei, A. Genome Biol. 2015