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Biochemical Society Transactions Oct 2023Diapause is a protective mechanism that many organisms deploy to overcome environmental adversities. Diapause extends lifespan and fertility to enhance the reproductive... (Review)
Review
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.
Topics: Animals; Humans; Diapause; Reproduction; Longevity
PubMed: 37800560
DOI: 10.1042/BST20221431 -
MedComm Dec 2023Emerging evidence indicates that cancer cells can mimic characteristics of embryonic development, promoting their development and progression. Cancer cells share... (Review)
Review
Emerging evidence indicates that cancer cells can mimic characteristics of embryonic development, promoting their development and progression. Cancer cells share features with embryonic development, characterized by robust proliferation and differentiation regulated by signaling pathways such as Wnt, Notch, hedgehog, and Hippo signaling. In certain phase, these cells also mimic embryonic diapause and fertilized egg implantation to evade treatments or immune elimination and promote metastasis. Additionally, the upregulation of ATP-binding cassette (ABC) transporters, including multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer-resistant protein (BCRP), in drug-resistant cancer cells, analogous to their role in placental development, may facilitate chemotherapy efflux, further resulting in treatment resistance. In this review, we concentrate on the underlying mechanisms that contribute to tumor development and progression from the perspective of embryonic development, encompassing the dysregulation of developmental signaling pathways, the emergence of dormant cancer cells, immune microenvironment remodeling, and the hyperactivation of ABC transporters. Furthermore, we synthesize and emphasize the connections between cancer hallmarks and embryonic development, offering novel insights for the development of innovative cancer treatment strategies.
PubMed: 38045829
DOI: 10.1002/mco2.427 -
Trends in Ecology & Evolution May 2024Insects have major impacts on forest ecosystems, from herbivory and soil-nutrient cycling to killing trees at a large scale. Forest insects from temperate, tropical, and... (Review)
Review
Insects have major impacts on forest ecosystems, from herbivory and soil-nutrient cycling to killing trees at a large scale. Forest insects from temperate, tropical, and subtropical regions have evolved strategies to respond to seasonality; for example, by entering diapause, to mitigate adversity and to synchronize lifecycles with favorable periods. Here, we show that distinct functional groups of forest insects; that is, canopy dwellers, trunk-associated species, and soil/litter-inhabiting insects, express a variety of diapause strategies, but do not show systematic differences in diapause strategy depending on functional group. Due to the overall similarities in diapause strategies, we can better estimate the impacts of anthropogenic change on forest insect populations and, consequently, on key ecosystems.
PubMed: 38777634
DOI: 10.1016/j.tree.2024.04.010 -
Current Opinion in Genetics &... Apr 2024Embryonic diapause in mammals is a period of developmental pause of the embryo at the blastocyst stage. During diapause, the blastocyst has minimal cell proliferation,... (Review)
Review
Embryonic diapause in mammals is a period of developmental pause of the embryo at the blastocyst stage. During diapause, the blastocyst has minimal cell proliferation, metabolic activity and gene expression. At reactivation, blastocyst development resumes, characterised by increases in cell number, biosynthesis and metabolism. Until recently, it has been unknown how diapause is maintained without any loss of blastocyst viability. This review focuses on recent progress in the identification of molecular pathways occurring in the blastocyst that can both cause and maintain the diapause state. A switch to lipid metabolism now appears essential to maintaining the diapause state and is induced by forkhead box protein O1. The forkhead box protein O transcription family is important for diapause in insects, nematodes and fish, but this is the first time a conclusive role has been established in mammals. Multiple epigenetic modifications are also essential to inducing and maintaining the diapause state, including both DNA and RNA methylation mechanisms. Finally, it now appears that diapause embryos, dormant stem cells and chemotherapeutic-resistant cancer cells may all share a universal system of quiescence.
PubMed: 38604005
DOI: 10.1016/j.gde.2024.102192 -
Integrative Organismal Biology (Oxford,... 2023In high-latitude environments where seasonal changes include periods of harsh conditions, many arthropods enter diapause, a period of dormancy that is hormonally...
In high-latitude environments where seasonal changes include periods of harsh conditions, many arthropods enter diapause, a period of dormancy that is hormonally regulated. Diapause is characterized by very low metabolism, resistance to environmental stress, and developmental arrest. It allows an organism to optimize the timing of reproduction by synchronizing offspring growth and development with periods of high food availability. In species that enter dormancy as pre-adults or adults, termination of diapause is marked by the resumption of physiological processes, an increase in metabolic rates and once transitioned into adulthood for females, the initiation of oogenesis. In many cases, individuals start feeding again and newly acquired resources become available to fuel egg production. However, in the subarctic capital-breeding copepod , feeding is decoupled from oogenesis. Thus, optimizing reproduction limited by fixed resources such that all eggs are of high quality and fully-provisioned, requires regulation of the number of oocytes. However, it is unknown if and how this copepod limits oocyte formation. In this study, the phase in oocyte production by post-diapause females that involved DNA replication in the ovary and oviducts was examined using incubation in 5-Ethynyl-2'-deoxyuridine (EdU). Both oogonia and oocytes incorporated EdU, with the number of EdU-labeled cells peaking at 72 hours following diapause termination. Cell labeling with EdU remained high for two weeks, decreasing thereafter with no labeling detected by four weeks post diapause, and three to four weeks before spawning of the first clutch of eggs. The results suggest that oogenesis is sequential in with formation of new oocytes starting within 24 hours of diapause termination and limited to the first few weeks. Lipid consumption during diapause was minimal and relatively modest initially. This early phase in the reproductive program precedes mid-oogenesis and vitellogenesis 2, when oocytes increase in size and accumulate yolk and lipid reserves. By limiting DNA replication to the initial phase, the females effectively separate oocyte production from oocyte provisioning. A sequential oogenesis is unlike the income-breeder strategy of most copepods in which oocytes at all stages of maturation are found concurrently in the reproductive structures.
PubMed: 37361914
DOI: 10.1093/iob/obad020 -
Transcription Nov 2023can enter a diapause stage called "dauer" when it senses that the environment is not suitable for development. This implies a detour from the typical developmental... (Review)
Review
can enter a diapause stage called "dauer" when it senses that the environment is not suitable for development. This implies a detour from the typical developmental trajectory and requires a tight control of the developmental clock and a massive tissue remodeling. In the last decades, core components of the signaling pathways that govern the dauer development decision have been identified, but the tissues where they function for the acquisition of dauer-specific traits are still under intense study. Growing evidence demonstrates that these pathways engage in complex cross-talk and feedback loops. In this review, we summarize the current knowledge regarding the transcriptional regulation of the dauer program and the relevant tissues for its achievement. A better understanding of this process will provide insight on how developmental plasticity is achieved and how development decisions are under a robust regulation to ensure an all-or-nothing response. Furthermore, this developmental decision can also serve as a simplified model for relevant developmental disorders. AID Auxin Induced Degron DA dafachronic acid Daf-c dauer formation constitutive Daf-d dauer formation defective DTC Distal Tip Cells ECM modified extracellular matrix GPCRs G protein-coupled receptors IIS insulin/IGF-1 signaling ILPs insulin-like peptides LBD Ligand Binding Domain PDL4 Post Dauer L4 TGF-β transforming growth factor beta WT wild-type.
Topics: Animals; Caenorhabditis elegans Proteins; Caenorhabditis elegans; Signal Transduction; Gene Expression Regulation; Insulin
PubMed: 36951297
DOI: 10.1080/21541264.2023.2190295 -
ENeuro Jul 2023The balance between the degeneration and regeneration of damaged neurons depends on intrinsic and environmental variables. In nematodes, neuronal degeneration can be...
The balance between the degeneration and regeneration of damaged neurons depends on intrinsic and environmental variables. In nematodes, neuronal degeneration can be reversed by intestinal GABA and lactate-producing bacteria, or by hibernation driven by food deprivation. However, it is not known whether these neuroprotective interventions share common pathways to drive regenerative outcomes. Using a well established neuronal degeneration model in the touch circuit of the bacterivore nematode , we investigate the mechanistic commonalities between neuroprotection offered by the gut microbiota and hunger-induced diapause. Using transcriptomics approaches coupled to reverse genetics, we identify genes that are necessary for neuroprotection conferred by the microbiota. Some of these genes establish links between the microbiota and calcium homeostasis, diapause entry, and neuronal function and development. We find that extracellular calcium as well as mitochondrial MCU-1 and reticular SCA-1 calcium transporters are needed for neuroprotection by bacteria and by diapause entry. While the benefits exerted by neuroprotective bacteria require mitochondrial function, the diet itself does not affect mitochondrial size. In contrast, diapause increases both the number and length of mitochondria. These results suggest that metabolically induced neuronal protection may occur via multiple mechanisms.
Topics: Animals; Neuroprotection; Calcium; Caenorhabditis elegans; Diapause; Gastrointestinal Microbiome; Mitochondria
PubMed: 37385728
DOI: 10.1523/ENEURO.0424-22.2023 -
Current Research in Insect Science 2024Diapause is a form of internally-controlled dormancy that allows insects to avoid stressful conditions and periods of low food availability. Eastern spruce budworm (...
Diapause is a form of internally-controlled dormancy that allows insects to avoid stressful conditions and periods of low food availability. Eastern spruce budworm ( Clemens), like many cold-adapted insects, enter diapause well in advance of winter conditions, thus exposing them to elevated temperatures during fall that can deplete energy stores and impact post-diapause survival. We explored the impact of fall conditions on by manipulating the length of the fall period and exposure temperatures during the diapause initiation phase of second instar larvae in a factorial design. We exposed second instar larvae to four fall temperatures (10, 15, 20, and 25°C) and five exposure times (1, 2, 4, 6, and 10 weeks) prior to standardized diapause conditions. We measured metabolites (glycogen, glycerol, and protein) prior to and during diapause for a subset of individuals. We also measured post-diapause survival by quantifying emergence following diapause conditions for a subset of individuals. We found that long, warm fall conditions depleted glycogen content and lowered post-diapause survival. We also found that short, cool conditions impacted post-diapause survival, although glycogen content remained high. Our results showed that fall conditions have substantial fitness consequences to overwintering insects. Optimal fall conditions struck a balance between exposure time and temperature. Our findings point to a potentially adaptive reason for early diapause onset: that an undescribed, but temperature-sensitive process is occurring in larvae during the diapause initiation period that is essential for overwintering survival and successful post-diapause emergence.
PubMed: 38371385
DOI: 10.1016/j.cris.2024.100073 -
Cell Death Discovery Aug 2023Bromo- and extra-terminal domain (BET) inhibitors (BETi) have been shown to decrease tumor growth in preclinical models and clinical trials. However, toxicity and rapid... (Review)
Review
Bromo- and extra-terminal domain (BET) inhibitors (BETi) have been shown to decrease tumor growth in preclinical models and clinical trials. However, toxicity and rapid emergence of resistance have limited their clinical implementation. To identify state changes underlying acquisition of resistance to the JQ1 BETi, we reanalyzed single-cell RNAseq data from JQ1 sensitive and resistant SUM149 and SUM159 triple-negative breast cancer cell lines. Parental and JQ1-resistant SUM149 and SUM159 exhibited a stem cell-like and embryonic diapause (SCLED) cell state as well as a transitional cell state between the SCLED state that is present in both treatment naïve and JQ1 treated cells, and a number of JQ1 resistant cell states. A transitional cell state transcriptional signature but not a SCLED state transcriptional signature predicted worsened outcomes in basal-like breast cancer patients suggesting that transit from the SCLED state to drug-resistant states contributes to patient outcomes. Entry of SUM149 and SUM159 into the transitional cell state was characterized by elevated expression of the CD9 tetraspanin. Knockdown or inhibition of CD9-sensitized cells to multiple targeted and cytotoxic drugs in vitro. Importantly, CD9 knockdown or blockade sensitized SUM149 to JQ1 in vivo by trapping cells in the SCLED state and limiting transit to resistant cell states. Thus, CD9 appears to be critical for the transition from a SCLED state into treatment-resistant cell states and warrants exploration as a therapeutic target in basal-like breast cancer.
PubMed: 37542044
DOI: 10.1038/s41420-023-01586-9 -
Medicina (Kaunas, Lithuania) Jan 2024Cancer is one of the leading causes of death in the world. Various drugs have been developed to eliminate it but to no avail because a tumor can go into dormancy to... (Review)
Review
Cancer is one of the leading causes of death in the world. Various drugs have been developed to eliminate it but to no avail because a tumor can go into dormancy to avoid therapy. In the past few decades, tumor dormancy has become a popular topic in cancer therapy. Recently, there has been an important breakthrough in the study of tumor dormancy. That is, cancer cells can enter a reversible drug-tolerant persister (DTP) state to avoid therapy, but no exact mechanism has been found. The study of the link between the DTP state and diapause seems to provide an opportunity for a correct understanding of the mechanism of the DTP state. Completely treating cancer and avoiding dormancy by targeting the expression of key genes in diapause are possible. This review delves into the characteristics of the DTP state and its connection with embryonic diapause, and possible treatment strategies are summarized. The authors believe that this review will promote the development of cancer therapy.
Topics: Animals; Humans; Diapause; Neoplasms
PubMed: 38399515
DOI: 10.3390/medicina60020228