Molecular Regulators of Embryonic Diapause and Cancer Diapause-like State

Abstract

Embryonic diapause is an enigmatic state of dormancy that interrupts the normally tight connection between developmental stages and time. This reproductive strategy and state of suspended development occurs in mice, bears, roe deer, and over 130 other mammals and favors the survival of newborns. Diapause arrests the embryo at the blastocyst stage, delaying the post-implantation development of the embryo. This months-long quiescence is reversible, in contrast to senescence that occurs in aging stem cells. Recent studies have revealed critical regulators of diapause. These findings are important since defects in the diapause state can cause a lack of regeneration and control of normal growth. Controlling this state may also have therapeutic applications since recent findings suggest that radiation and chemotherapy may lead some cancer cells to a protective diapause-like, reversible state. Interestingly, recent studies have shown the metabolic regulation of epigenetic modifications and the role of microRNAs in embryonic diapause. In this review, we discuss the molecular mechanism of diapause induction.

Stress-induced reversible cell-cycle arrest requires PRC2/PRC1-mediated control of mitophagy in Drosophila germline stem cells and human iPSCs

“…In line with our data, the Pc homolog Cbx7 in African killifish has been recently shown to be required for maintaining diapause ( Hu et al., 2020 ). Furthermore, recent findings suggest that cancer-related irradiation and chemotherapy may lead a class of cancer cells (cancer stem cells, CSCs) to enter a protective, reversible diapause-like state ( Dhimolea et al., 2021 ; Rehman et al., 2021 ; Hussein et al., 2022 ). Hence, targeting the PRC1/2 complex ( Levy et al., 2022 ) might force cells to exit diapause-like quiescence in the normal, as well as the cancer, state, guiding CSCs to a proliferative stage amenable to conventional chemotherapies.…”

“…DNA damage checkpoint recognizes irreparable DNA damage, inducing p53-dependent apoptosis ( Aubrey et al., 2018 ; Speidel, 2010 ; Chakravarti et al., 2022 ; He et al., 2019 ). However, despite p53 activity ( Hussein et al., 2020 ; Ma et al., 2016 ), stem cells in quiescence, including embryonic stem cells (ESCs) in diapause, resist apoptosis ( Artoni et al., 2017 ; Hussein et al., 2020 , 2022 ; Arena et al., 2021 ; Xing et al., 2015 ; Ma et al., 2016 ). Although it is not understood mechanistically how stem cells in general avoid apoptosis, in the germline stem cells (GSCs) of the adult Drosophila ovary at least one protective mechanism has been identified.…”

KDM5D Histone Demethylase Identifies Platinum-Tolerant Head and Neck Cancer Cells Vulnerable to Mitotic Catastrophe

“…CSCs can undergo self-renewal within a tumor. Similar to normal stem cells, CSCs can become dormant when they are resistant to most anticancer treatments, including chemotherapy, and can contribute to tumor recurrence [ 12 ]. Thus, identifying a common regulator (such as KDM5D ) of cancer stemness, a diapause-like state, and treatment resistance may help in the development of a strategy for targeting drug-tolerant persister HNSCC cells.…”

“…DTPCs have distinct stemness characteristics, slow-cycling profile, quiescent behavior, and diapause-state-like properties [ 10 , 11 ]. The diapause state represents a dormant, non-proliferating subset of cancer cells, mimicking embryonic development to prevent an exogenous insult, in this case, chemotherapy-induced cell death [ 12 ]. These distinct features can result from the selection of existing intrinsically refractory clones or adaptive transcriptional plasticity–driven mechanisms during treatment [ 10 ].…”

Unveiling the role of cellular dormancy in cancer progression and recurrence

“…Furthermore, cellular dormancy constitutes a widespread survival strategy against adverse environments. One of the most striking examples of such an adjustment in nature is diapause, in which species reversibly suspend their embryonic development, sometimes for several months, if environmental conditions are unfavorable for embryo growth and maturation [31][32][33]. Phenotypic and transcriptional parallels have been drawn between diapause and various models of cancer dormancy, implying that tumors may be 'hijacking' an evolutionarily conserved mechanism [11,19,32,34,35].…”