Regulation Of Dormancy Research Articles

Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide?

Many solid tumors including breast cancer can exhibit early dissemination and dormancy-in which cancer cells spread early in the disease process and survive long periods without detectable growth. These early disseminated tumor cells sometimes reactivate and lead to incurable metastatic disease years or even decades after curative-intent therapy for the primary tumor. We are just beginning to understand the role of the immune system in this process in part because of improvements in immunocompetent models as well as technological advances such as single-cell genomics and spatial transcriptomics. In this issue of Cancer Research, Bushnell and colleagues showed that NK cells are important in this context. The authors found that disseminated tumor cells and quiescent cells express higher levels of MHC 1 but are resistant to NK-cell-mediated immunity. The proposed mechanism involves the STING pathway and transcription factors Sox2 and Bach1. As other studies have highlighted the importance of T-cell immunity, this work reaffirms the importance and diversity of immune regulation of dormancy and suggests the need for future studies to flesh out mechanistic details and predict when each type of immunity is most important. See related article by Bushnell et al., p. 3337.

AINTEGUMENTA-LIKE genes regulate reproductive growth and bud dormancy in Platanus acerifolia.

Platanus acerifolia AIL genes PaAIL5a/b and PaAIL6b participate in FT-AP1/FUL-AIL pathways to regulate bud dormancy. In addition, PaAIL6a/b can promote flowering, and PaAIL5b and PaAIL6b affect floral development. Bud dormancy and floral induction are essential processes for perennial plants, they are both regulated by photoperiod, temperature, and hormones, indicating the existence of common regulators for both processes. AINTEGUMENTA-LIKE (AIL) genes regulate reproductive growth of annual plants, including floral induction and flower development, and their homologs in poplar and grape act downstream of the florigen gene FT and the floral meristem identity genes AP1/FUL and function to maintain growth and thus inhibit dormancy induction. However, it is not known whether AIL homologs participate in the reproduction processes in perennials and whether the Platanus acerifolia AIL genes are involved in dormancy. P. acerifolia is a perennial woody plant whose reproductive growth is strongly associated with dormancy. Here, we isolated four AIL homologs from P. acerifolia, PaAIL5a, PaAIL5b, PaAIL6a, and PaAIL6b, and systematically investigated their functions by ectopic-overexpression in tobacco. The findings demonstrate that PaAIL5a/b and PaAIL6b respond to short day, low temperature, and hormone signals and act as the components of the FT-AP1/FUL-AIL pathway to regulate the bud dormancy in P. acerifolia. Notably, PaAIL5a/b and PaAIL6b function downstream of PaFTL-PaFUL1/2/3 to inhibit the dormancy induction and downstream of PaFT-PaFUL2/3 to promote the dormancy release. In addition, PaAIL6a/b were found to accelerate flowering in transgenic tobacco, whereas PaAIL5b and PaAIL6b affected the flower development. Together, our results suggest that PaAIL genes may act downstream of different PaFT/PaFTL and PaFUL proteins to fulfill conservative and diverse roles in floral initiation, floral development, and dormancy regulation in P. acerifolia.

Dormancy regulator Prunus mume DAM6 promotes ethylene-mediated leaf senescence and abscission.

Leaf senescence and abscission in autumn are critical phenological events in deciduous woody perennials. After leaf fall, dormant buds remain on deciduous woody perennials, which then enter a winter dormancy phase. Thus, leaf fall is widely believed to be linked to the onset of dormancy. In Rosaceae fruit trees, DORMANCY-ASSOCIATED MADS-box (DAM) transcription factors control bud dormancy. However, apart from their regulatory effects on bud dormancy, the biological functions of DAMs have not been thoroughly characterized. In this study, we revealed a novel DAM function influencing leaf senescence and abscission in autumn. In Prunus mume, PmDAM6 expression was gradually up-regulated in leaves during autumn toward leaf fall. Our comparative transcriptome analysis using two RNA-seq datasets for the leaves of transgenic plants overexpressing PmDAM6 and peach (Prunus persica) DAM6 (PpeDAM6) indicated Prunus DAM6 may up-regulate the expression of genes involved in ethylene biosynthesis and signaling as well as leaf abscission. Significant increases in 1-aminocyclopropane-1-carboxylate accumulation and ethylene emission in DEX-treated 35S:PmDAM6-GR leaves reflect the inductive effect of PmDAM6 on ethylene biosynthesis. Additionally, ethephon treatments promoted autumn leaf senescence and abscission in apple and P. mume, mirroring the changes due to PmDAM6 overexpression. Collectively, these findings suggest that PmDAM6 may induce ethylene emission from leaves, thereby promoting leaf senescence and abscission. This study clarified the effects of Prunus DAM6 on autumn leaf fall, which is associated with bud dormancy onset. Accordingly, in Rosaceae, DAMs may play multiple important roles affecting whole plant growth during the tree dormancy induction phase.

Natural Killer Cell Regulation of Breast Cancer Stem Cells Mediates Metastatic Dormancy.

Patients with breast cancer with estrogen receptor-positive tumors face a constant risk of disease recurrence for the remainder of their lives. Dormant tumor cells residing in tissues such as the bone marrow may generate clinically significant metastases many years after initial diagnosis. Previous studies suggest that dormant cancer cells display "stem-like" properties (cancer stem cell, CSC), which may be regulated by the immune system. To elucidate the role of the immune system in controlling dormancy and its escape, we studied dormancy in immunocompetent, syngeneic mouse breast cancer models. Three mouse breast cancer cell lines, PyMT, Met1, and D2.0R, contained CSCs that displayed short- and long-term metastatic dormancy in vivo, which was dependent on the host immune system. Each model was regulated by different components of the immune system. Natural killer (NK) cells were key for the metastatic dormancy phenotype in D2.0R cells. Quiescent D2.0R CSCs were resistant to NK cell cytotoxicity, whereas proliferative CSCs were sensitive. Resistance to NK cell cytotoxicity was mediated, in part, by the expression of BACH1 and SOX2 transcription factors. Expression of STING and STING targets was decreased in quiescent CSCs, and the STING agonist MSA-2 enhanced NK cell killing. Collectively, these findings demonstrate the role of immune regulation of breast tumor dormancy and highlight the importance of utilizing immunocompetent models to study this phenomenon. Significance: The immune system controls disseminated breast cancer cells during disease latency, highlighting the need to utilize immunocompetent models to identify strategies for targeting dormant cancer cells and reducing metastatic recurrence. See related commentary by Cackowski and Korkaya, p. 3319.

Functional evidence on the involvement of the MADS-box gene MdDAM4 in bud dormancy regulation in apple.

Over the course of the year, temperate trees experience extremes in temperature and day length. In order to protect themselves from frost damage in winter, they enter a dormant state with no visible growth where all leaves are shed and buds are dormant. Also the young floral tissues need to withstand harsh winter conditions, as temperature fruit trees like apple develop their flower buds in the previous year of fruit development. So far, the genetic control of induction and release of dormancy is not fully understood. However, the transcription factor family of DORMANCY-Associated MADS-box (DAM) genes plays a major role in the control of winter dormancy. One of these genes is MdDAM4. This gene is expressed in the early phase of bud dormancy, but little is known about its function. Six transgenic apple lines were produced to study the function of MdDAM4 in apple. For plant transformation, the binary plasmid vector p9oN-35s-MdDAM4 was used that contains the coding sequence of MdDAM4 driven by the 35S promoter. Transgenicity of the lines was proven by PCR and southern hybridization. Based on siRNA sequencing and phenotypic observations, it was concluded that line M2024 overexpresses MdDAM4 whereas the gene is silenced in all other lines. Phenotyping of the transgenic lines provided evidence that the overexpression of MdDAM4 leads to an earlier induction and a later release of dormancy. Silencing this gene had exactly the opposite effects and thereby led to an increased duration of the vegetation period. Expression experiments revealed genes that were either potentially repressed or activated by MdDAM4. Among the potentially suppressed genes were several homologs of the cytokinin oxidase 5 (CKX5), five LOX homologs, and several expansins, which may indicate a link between MdDAM4 and the control of leaf senescence. Among the potentially activated genes is MdDAM1, which is in line with observed expression patterns during winter dormancy. MdDAM2, which shows little expression during endodormancy also appears to be activated by MdDAM4. Overall, this study provides experimental evidence with transgenic apple trees for MdDAM4 being an important regulator of the onset of bud dormancy in apple.

Bone niches in the regulation of tumour cell dormancy

Secondary metastases, accounting for 90 % of cancer-related deaths, pose a formidable challenge in cancer treatment, with bone being a prevalent site. Importantly, tumours may relapse, often in the skeleton even after successful eradication of the primary tumour, indicating that tumour cells may lay dormant within bone for extended periods of time. This review summarises recent findings in the mechanisms underlying tumour cell dormancy and the role of bone cells in this process. Hematopoietic stem cell (HSC) niches in bone provide a model for understanding regulatory microenvironments. Dormant tumour cells have been shown to exploit similar niches, with evidence suggesting interactions with osteoblast-lineage cells and other stromal cells via CXCL12-CXCR4, integrins, and TAM receptor signalling, especially through GAS6-AXL, led to dormancy, with exit of dormancy potentially regulated by osteoclastic bone resorption and neuronal signalling. A comprehensive understanding of dormant tumour cell niches and their regulatory mechanisms is essential for developing targeted therapies, a critical step towards eradicating metastatic tumours and stopping disease relapse.

The MKK3 MAPK cascade integrates temperature and after-ripening signals to modulate seed germination

The timing of seed germination is controlled by the combination of internal dormancy and external factors. Temperature is a major environmental factor for seed germination. The permissive temperature range for germination is narrow in dormant seeds and expands during after-ripening (AR) (dormancy release). Quantitative trait loci analyses of preharvest sprouting in cereals have revealed that MKK3, a mitogen-activated protein kinase (MAPK) cascade protein, is a negative regulator of grain dormancy. Here, we show that the MAPKKK19/20-MKK3-MPK1/2/7/14 cascade modulates the germination temperature range in Arabidopsis seeds by elevating the germinability of the seeds at sub- and supraoptimal temperatures. The expression of MAPKKK19 and MAPKKK20 is induced around optimal temperature for germination in after-ripened seeds but repressed in dormant seeds. MPK7 activation depends on the expression levels of MAPKKK19/20, with expression occurring under conditions permissive for germination. Abscisic acid (ABA) and gibberellin (GA) are two major phytohormones which are involved in germination control. Activation of the MKK3 cascade represses ABA biosynthesis enzyme gene expression and induces expression of ABA catabolic enzyme and GA biosynthesis enzyme genes, resulting in expansion of the germinable temperature range. Our data demonstrate that the MKK3 cascade integrates temperature and AR signals to phytohormone metabolism and seed germination.

SlWRKY37 targets SlLEA2 and SlABI5-like7 to regulate seed germination vigor in tomato

Seed germination is a critical phase for the life cycle and propagation of higher plants. This study explores the role of SlWRKY37, a WRKY transcription factor in tomato, in modulating seed germination. We discovered that SlWRKY37 expression is markedly downregulated during tomato seed germination. Through CRISPR/Cas9-mediated editing, we demonstrate that SlWRKY37 knockout enhances germination, while its overexpression results in a delay compared to the wild type. Transcriptome analysis revealed 679 up-regulated and 627 down-regulated genes in Slwrky37-CRISPR deletion mutants relative to the wild type. Gene ontology (GO) enrichment analysis indicated these differentially expressed genes are linked to seed dormancy, abscisic acid homeostasis, and protein phosphorylation pathways. Bioinformatics and biochemical assays identified SlABI5-like7 and SlLEA2 as key transcriptional targets of SlWRKY37, integral to tomato seed dormancy regulation. Additionally, SlWRKY37 was found to be post-translationally phosphorylated at Ser65, a modification crucial for its transcriptional activation. Our findings elucidate the regulatory role of SlWRKY37 in seed dormancy, suggesting its potential as a target for gene editing to reduce seed dormancy in tomato breeding programs.

PsSOC1 is involved in the gibberellin pathway to trigger cell proliferation and budburst during endodormancy release in tree peony.

Tree peony (Paeonia suffruticosa) undergoes bud endodormancy, and gibberellin (GA) pathway plays a crucial role in dormancy regulation. Recently, a key DELLA protein PsRGL1 has been identified as a negative regulator of bud dormancy release. However, the mechanism of GA signal to break bud dormancy remains unknown. In this study, yeast two-hybrid screened PsSOC1 interacting with PsRGL1 through its MADS domain, and interaction was identified using pull-down and luciferase complementation imaging assays Transformation in tree peony and hybrid poplar confirmed that PsSOC1 facilitated bud dormancy release. Transcriptome analysis of PsSOC1-overexpressed buds indicated PsCYCD3.3 and PsEBB3 were its potential downstream targets combining with promoter survey, and they also accelerated bud dormancy release verified by genetic analysis. Yeast one-hybrid, electrophoretic mobility shifts assays, chromatin immunoprecipitation quantitative PCR, and dual luciferase assays confirmed that PsSOC1 could directly bind to the CArG motif of PsCYCD3.3 and PsEBB3 promoters via its MADS domain. PsRGL1-PsSOC1 interaction inhibited the DNA-binding activity of PsSOC1. Additionally, PsCYCD3.3 promoted bud dormancy release by rebooting cell proliferation. These findings elucidated a novel GA pathway, GA-PsRGL1-PsSOC1-PsCYCDs, which expanded our understanding of the GA pathway in bud dormancy release.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Identification of ARF Genes and Elucidation of the Regulatory Effects of PsARF16a on the Dormancy of Tree Peony Plantlets.

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator of tree peony dormancy. To clarify the mechanism mediating tree peony plantlet dormancy, PsARF genes were systematically identified and analyzed. Additionally, PsARF16a was transiently expressed in the leaves of tree peony plantlets to examine its regulatory effects on a downstream gene network. Nineteen PsARF genes were identified and divided into four classes. All PsARF genes encoded proteins with conserved B3 and ARF domains. The number of motifs, exons, and introns varied between PsARF genes in different classes. The overexpression of PsARF16a altered the expression of NCED, ZEP, PYL, GA2ox1, GID1, and other key genes in abscisic acid (ABA) and gibberellin (GA) signal transduction pathways, thereby promoting ABA synthesis and decreasing GA synthesis. Significant changes to the expression of some key genes contributing to starch and sugar metabolism (e.g., AMY2A, BAM3, BGLU, STP, and SUS2) may be associated with the gradual conversion of sugar into starch. This study provides important insights into PsARF functions in tree peonies.

Emerging into the world: regulation and control of dormancy and sprouting in geophytes.

Geophytic plants synchronize growth and quiescence with the external environment to survive and thrive under changing seasons. Together with seasonal growth adaptation, dormancy and sprouting are critical factors determining crop yield and market supply, as various geophytes also serve as major food, floriculture, and ornamental crops. Dormancy in such crops determines crop availability in the market, as most of them are consumed during the dormant stage. On the other hand, uniform/maximal sprouting is crucial for maximum yield. Thus, dormancy and sprouting regulation have great economic importance. Dormancy-sprouting cycles in geophytes are regulated by genetic, exogenous (environmental), and endogenous (genetic, metabolic, hormonal, etc.) factors. Comparatively, the temperature is more dominant in regulating dormancy and sprouting in geophytes, unlike above-ground tissues, where both photoperiod and temperature control are involved. Despite huge economic importance, studies concerning the regulation of dormancy and sprouting are scarce in the majority of geophytes. To date, only a few molecular factors involved in the process have been suggested. Recently, omics studies on molecular and metabolic factors involved in dormancy and growth regulation of underground vegetative tissues have provided more insight into the mechanism. Here, we discuss current knowledge of the environmental and molecular regulation and control of dormancy and sprouting in geophytes, and discuss challenges/questions that need to be addressed in the future for crop improvement.

Physiological and molecular mechanisms associated with potato tuber dormancy.

Tuber dormancy is an important physiological trait that impacts post-harvest storage and end-use qualities of potatoes. Overall, dormancy regulation of potato tubers is a complex process driven by genetic as well as environmental factors. Elucidation of the molecular and physiological mechanisms that influence different dormancy stages of tubers has wider potato breeding and industry-relevant implications. Therefore, the primary objective of this review is to present current knowledge of the diversity in tuber dormancy traits among wild relatives of potatoes and discuss how genetic and epigenetic factors contribute to tuber dormancy. Advancements in understanding of key physiological mechanisms involved in tuber dormancy regulation, such as apical dominance, phytohormone metabolism, and oxidative stress responses, are also discussed. This review highlights the impacts of common sprout suppressors on the molecular and physiological mechanisms associated with tuber dormancy and other storage qualities. Collectively, the literature suggests that significant changes in expression of genes associated with the cell cycle, phytohormone metabolism, and oxidative stress response influence initiation, maintenance, and termination of dormancy in potato tubers. Commercial sprout suppressors mainly alter the expression of genes associated with the cell cycle and stress responses and suppress sprout growth rather than prolonging tuber dormancy.

Identification of a key signaling network regulating perennating bud dormancy in Panax ginseng

BackgroundThe cycle of seasonal dormancy of perennating buds is an essential adaptation of perennial plants to unfavorable winter conditions. Plant hormones are key regulators of this critical biological process, which is intricately connected with diverse internal and external factors. Recently, global warming has increased the frequency of aberrant temperature events that negatively affect the dormancy cycle of perennials. Although many studies have been conducted on the perennating organs of Panax ginseng, the molecular aspects of bud dormancy in this species remain largely unknown. MethodsIn this study, the molecular physiological responses of three P. ginseng cultivars with different dormancy break phenotypes in the spring were dissected using comparative genome-wide RNA-seq and network analyses. These analyses identified a key role for abscisic acid (ABA) activity in the regulation of bud dormancy. Gene set enrichment analysis revealed that a transcriptional network comprising stress-related hormone responses made a major contribution to the maintenance of dormancy. ResultsIncreased expression levels of cold response and photosynthesis-related genes were associated with the transition from dormancy to active growth in perennating buds. Finally, the expression patterns of genes encoding ABA transporters, receptors (PYRs/PYLs), PROTEIN PHOSPHATASE 2Cs (PP2Cs), and DELLAs were highly correlated with different dormancy states in three P. ginseng cultivars. ConclusionThis study provides evidence that ABA and stress signaling outputs are intricately connected with a key signaling network to regulate bud dormancy under seasonal conditions in the perennial plant P. ginseng.

Abstract 5540: Single cell multiomic analysis of human brain metastasis reveals conserved dormancy population

Abstract This study explores the complex realm of brain metastasis, pivotal in crafting effective anti-tumor strategies. Leveraging single-cell multi-omics sequencing, we profiled the transcriptomes and chromatin accessibility landscapes of tumor cells and their surrounding microenvironment in human brain metastases that originated from across a spectrum of primary cancers. Our investigations have identified distinct, yet uniformly present, tumor cell subpopulations, each defined by unique gene expression patterns, chromatin accessibility, and the interactions between tumor and stromal cells. Notably, one such subpopulation exhibits a dormancy signature, characterized by enhanced interferon response, oxidative phosphorylation, and upregulated HLA class molecules, alongside alterations in circadian rhythms. Our trajectory analysis charts a course from these dormant cells to rapidly proliferating ones, with notable shifts in circadian rhythm genes, underscoring their potential role in brain metastasis. This aligns with recent findings that disruptions in circadian rhythms can modify stem cell characteristics in glioblastomas. This insight led us to focus on a specific circadian rhythm gene, highly active in the dormant cells and located on the HER2 amplicon—an area linked to high brain metastasis relapse rates in patients. We've developed inducible models for both overexpression and knockdown to scrutinize this gene's impact in her2 positive breast cancer cell lines, examining gene expression and proliferation in vitro. Complementing this, we are conducting spatial transcriptomic analysis to evaluate the microenvironmental regulation of tumor dormancy in human brain metastases. This multi-omics approach reveals a nuanced regulatory landscape of brain metastasis, highlighting a novel and often overlooked factor in metastasis progression and brain tumor relapse: the interplay between circadian rhythms and tumor dormancy. This discovery not only deepens our understanding of brain metastases but also opens potential new avenues for therapeutic interventions. Citation Format: Remi Klotz, Yiru Wang, Anu Sunkara, Frank Attenelo, Min Yu. Single cell multiomic analysis of human brain metastasis reveals conserved dormancy population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5540.

Abstract 5539: PRDM16 is an intrinsic regulator of dormancy in bone disseminated prostate cancer cells

Abstract Metastatic prostate cancer (PCa) frequently occurs in the bone and can remain inactive for extended periods after primary tumor treatment. Understanding the intricate molecular mechanisms that govern this phenomenon could open the door to novel therapies, potentially reducing mortality rates. To address this, we developed a novel protocol to induce cellular dormancy in PCa cell lines (RM1, 22Rv1, LAPC4) in vitro. We noted that dormant cells exhibited distinctive clustering and could be reactivated when exposed to serum even after 21 days of stasis. The dormancy program was validated by multiple assays including cell cycle analysis, membrane dye retention, and Edu+ incorporation. RNASeq analysis showed significant transcriptional changes during dormancy induction, with 8 genes commonly upregulated across multiple human and mouse PCa cell lines, of which the transcription factor, PRDM16. We focused on PRDM16 since, 1) it is a known regulator of hematopoietic stem cell quiescence, 2) our emerging data points to bone morphogenetic protein-7 (BMP7), a well-known exogenous mediator of dormancy as an inducer of PRDM16 expression and 3) clinically, PRDM16 is suppressed in primary PCa and active metastases. First, we validated the upregulation of PRDM16 during dormancy in vitro. Silencing PRDM16 led to impaired dormancy phenotype and cell death, while its overexpression significantly mitigated proliferation rates and promoted survival. In vivo, we employed an intra-iliac immunocompetent model (RM1 & C57BL6J) and demonstrated that overexpressing PRDM16 in active RM1 cells resulted in significant reduction of metastasis formation and Ki67 expression concurrent with extended survival when injected in vivo compared to control cells. Prostate cancer cells with PRDM16 over-expression were detected in bone sections as solitary or small clusters (<20 cells) demonstrating an inverse relationship between PRDM16 expression and metastatic outbreak. In defining the targets via which PRDM16 controls dormancy entry, we focused on RAR related orphan receptor C (RORC) based on bioinformatic analysis and publicly available PRDM16 ChIP-Seq. Our data demonstrate that pharmacological inhibition of RORC using GSK805 promoted the apoptosis of dormant PCa cells specifically when compared to their actively growing counterparts. In conclusion, our studies have revealed the critical role of PRDM16 in promoting PCa cell dormancy, in part via upregulating RORC. Translationally, clinically approved RORC inhibitors for non-cancerous conditions (psoriasis) have been developed. We expect, based on our results, that these inhibitors could be repurposed for the eradication of dormant PCa cells in patients with advanced disease. Citation Format: Mostafa M. Nasr, Tao Li, Ryan T. Bishop, Jeremy S. Frieling, Conor C. Lynch. PRDM16 is an intrinsic regulator of dormancy in bone disseminated prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5539.

Comparative genomics of N-acetyl-5-methoxytryptamine members in four Prunus species with insights into bud dormancy and abiotic stress responses in Prunus avium.

This study provides novel insights into the evolution, diversification, and functions of melatonin biosynthesis genes in Prunus species, highlighting their potential role in regulating bud dormancy and abiotic stresses. The biosynthesis of melatonin (MEL) in plants is primarily governed by enzymatic reactions involving key enzymes such as serotonin N-acetyltransferase (SNAT), tryptamine 5-hydroxylase (T5H), N-acetylserotonin methyltransferase (ASMT) and tryptophan decarboxylase (TDC). In this study, we analyzed Melatonin genes in four Prunus species such as Prunus avium (Pavi), Prunus pusilliflora (Ppus), Prunus serulata (Pser), and Prunus persica (Pper) based on comparative genomics approach. Among the four Prunus species, a total of 29 TDCs, 998 T5Hs, 16 SNATs, and 115 ASMTs within the genome of four Prunus genomes. A thorough investigation of melatonin-related genes was carried out using systematic biological methods and comparative genomics. Through phylogenetic analysis, orthologous clusters, Go enrichment, syntenic relationship, and gene duplication analysis, we discovered both similarities and variations in Melatonin genes among these Prunus species. Additionally, our study revealed the existence of unique subgroup members in the Melatonin genes of these species, which were distinct from those found in Arabidopsis genes. Furthermore, the transcriptomic expression analysis revealed the potential significance of melatonin genes in bud dormancy regulation and abiotic stresses. Our extensive results offer valuable perspectives on the evolutionary patterns, intricate expansion, and functions of PavMEL genes. Given their promising attributes, PavTDCs, PavT5H, PavNAT, and three PavASMT genes warrant in-depth exploration as prime candidates for manipulating dormancy in sweet cherry. This was done to lay the foundation for future explorations into the structural and functional aspects of these factors in Prunus species. This study offers significant insights into the functions of ASMT, SNAT, T5H, and TDC genes and sheds light on their roles in Prunus avium. Moreover, it established a robust foundation for further exploration functional characterization of melatonin genes in fruit species.

Thermal regulation of dormancy in Echinochloa crus‐galli (L.) P. Beauv. seeds: Development of a model to predict the temporal ‘window’ of emergence in the field

AbstractPredicting weed emergence is of vital importance for weed management, since the seedling stage is the most effective plant stage for the application of control practices. In weeds species whose seeds present dormancy, as in Echinochloa crus‐galli, predicting emergence requires understanding how the environment regulates seed dormancy level. In the present work we studied the environmental regulation of dormancy in E. crus‐galli seeds. For this, E. crus‐galli seeds were stored under different conditions: (i) moist at 5, 10 and 15°C (stratification) and (ii) dry at 15 and 25°C (dry after‐ripening) for 80 days. During storage the seeds were tested for germination at regular intervals under a wide thermal range (10–30°C). The results showed that the changes in dormancy level were associated with a widening of the thermal range permissive for seed germination, which was mainly explained by a decrease in its lower limit temperature (Tl). This decrease in Tl was higher when the seeds were stratified at 10°C than at 5 and 15°C. Seeds exposed to dry after‐ripening showed an extremely low rate of dormancy release. Obtained results were used to establish functional relationships able to predict the temporal ‘window’ of field emergence of E. crus‐galli as a function of soil temperature.

Screening and Expression Analysis of POD Gene in POD-H2O2 Pathway on Bud Dormancy of Pear (Pyrus pyrifolia)

Bud endodormancy represents a pivotal and intricate biological process influenced by both genetic and epigenetic factors, the exact mechanism of which remains elusive. Hydrogen peroxide (H2O2) functions as a signalling molecule in the regulation of dormancy, with peroxidase (POD) playing a crucial role in governing H2O2 levels. Our prior transcriptomic and metabolomic investigations into diverse pear dormancy phases posited that POD predominantly oversees pear bud dormancy. In this study, we utilised qRT-PCR to screen the most significantly expressed gene, Pyrus pyrifolia POD4-like (PpPOD4-like), from seven POD genes. Subsequently, H2O2 test kits, overexpression methods, and subcellular localisation techniques were employed to assess changes in H2O2 content, POD activity, PpPOD4-like expression, and its cellular positioning during pear bud dormancy. Subcellular localisation experiments revealed that PpPOD4-like is situated on the cell membranes. Notably, H2O2 content exhibited a rapid increase during endodormancy and decreased swiftly after ecodormancy. The fluctuation pattern of POD activity aligned with that of H2O2 content. Additionally, PpPOD4-like expression was markedly upregulated, displaying an overall upward trajectory. Our findings indicate that PpPOD4-like modulates H2O2 levels by regulating POD activity, thereby actively participating in the intricate regulation of pear dormancy processes.

A commitment for life: Decades of unraveling the molecular mechanisms behind seed dormancy and germination.

Seeds are unique time capsules that can switch between 2 complex and highly interlinked stages: seed dormancy and germination. Dormancy contributes to the survival of plants because it allows to delay germination to optimal conditions. The switch between dormancy and germination occurs in response to developmental and environmental cues. In this review we provide a comprehensive overview of studies that have helped to unravel the molecular mechanisms underlying dormancy and germination over the last decades. Genetic and physiological studies provided a strong foundation for this field of research and revealed the critical role of the plant hormones abscisic acid and gibberellins in the regulation of dormancy and germination, and later natural variation studies together with quantitative genetics identified previously unknown genetic components that control these processes. Omics technologies like transcriptome, proteome, and translatomics analysis allowed us to mechanistically dissect these processes and identify new components in the regulation of seed dormancy and germination.