The molecular mechanisms of diapause and diapause-like reversible arrest

Abstract

Diapause is a protective mechanism that many organisms deploy to overcome environmental adversities. Diapause extends lifespan and fertility to enhance the reproductive success and survival of the species. Although diapause states have been known and employed for commercial purposes, for example in the silk industry, detailed molecular and cell biological studies are an exciting frontier. Understanding diapause-like protective mechanisms will shed light on pathways that steer organisms through adverse conditions. One hope is that an understanding of the mechanisms that support diapause might be leveraged to extend the lifespan and/or health span of humans as well as species threatened by climate change. In addition, recent findings suggest that cancer cells that persist after treatment mimic diapause-like states, implying that these programs may facilitate cancer cell survival from chemotherapy and cause relapse. Here, we review the molecular mechanisms underlying diapause programs in a variety of organisms, and we discuss pathways supporting diapause-like states in tumor persister cells.

Keywords: chemotherapy; diapause; dormancy; germline stem cell; quiescence; stem cell self-renewal.

Figure 1.. Diapause/diapause-like state to survive adverse conditions.

Animals or cells sense the environmental cues or chemo-drug treatment and transform into a protective stress-resistant state to evade the harsh conditions. Once the adverse conditions reverse, they can then recover and restart the development or the proliferation. The extent of reversibility depends on the duration and intensity of the adverse conditions prevailing, and the sooner the optimal conditions arrive better the reversibility.

Figure 2.. Diapause/diapause-like state protects stem cell longevity.

Stem cells undertake a reversible quiescence and evade the adverse conditions to avoid senescence and decline to keep a youthful state. Post-diapause, the stem cells reverse the quiescence and resume proliferation and self-renewal.

Figure 3.. Tumor cells mimic diapause-like state to persist chemotherapy.

Tumor cells take up an inactive diapause-like state to survive the chemotherapy. Once the drug is withdrawn, the persister cells can often resurge back later in life.