Genetic Rescue Research Articles

Montane willow scrub restoration in Scotland: reviewing 30 years of progress to reestablish the altitudinal treeline

Many mountain woodlands across the globe have undergone anthropogenic degradation with negative implications for the ecological and socioeconomic systems dependent on them. Montane willows are arctic‐alpine species of high nature conservation concern within the altitudinal treeline. Scotland has been pioneering the restoration of montane willow scrub for three decades following widespread loss linked particularly to overgrazing by sheep and deer since the eighteenth century. In the 1990s, the total area of montane willows throughout the country was less than 10 ha, with most remaining populations highly fragmented, in rapid decline, and restricted to inaccessible cliffs. Subsequently, montane willow scrub restoration has been part of an overall 2659 ha area managed for the recovery of mountain woodlands in Scotland. By May 2023, 396,868 montane willows were planted in projects encompassing large‐scale habitat creation, relict population reinforcement by genetic rescue, fencing, and landscape‐scale management for low‐density deer populations. This review summarizes restoration methods and outcomes with case study examples to promote conservation evidence and research on plant growth and survival, planting sites, associated biodiversity, molecular ecology, genomics, and long‐term population sustainability. With the potential for montane scrub restoration to be widely expanded, improved connectivity to revive a treeline mosaic shaped by regeneration will tackle biodiversity loss and help mitigate climate change impacts on a national scale. However, caution must be applied to creating definitions of distinct habitats for restoration that are based on non‐natural or ecologically degraded systems. These experiences are particularly relevant to montane and circumpolar regions with strongly modified landscape histories.

Limited Migration From Physiological Refugia Constrains the Rescue of Native Gastropods Facing an Invasive Predator.

Biological invasions have caused the loss of freshwater biodiversity worldwide. The interplay between adaptive responses and demographic characteristics of populations impacted by invasions is expected to be important for their resilience, but the interaction between these factors is poorly understood. The freshwater gastropod Amnicola limosus is native to the Upper St. Lawrence River and distributed along a water calcium concentration gradient within which high-calcium habitats are impacted by an invasive predator fish (Neogobius melanostomus, round goby), whereas low-calcium habitats provide refuges for the gastropods from the invasive predator. Our objectives were to (1) test for adaptation of A. limosus to the invasive predator and the low-calcium habitats, and (2) investigate if migrant gastropods could move from refuge populations to declining invaded populations (i.e., demographic rescue), which could also help maintain genetic diversity through gene flow (i.e., genetic rescue). We conducted a laboratory reciprocal transplant of wild F0 A. limosus sourced from the two habitat types (high calcium/invaded and low calcium/refuge) to measure adult survival and fecundity in home and transplant treatments of water calcium concentration (low/high) and round goby cue (present/absent). We then applied pooled whole-genome sequencing of 12 gastropod populations from across the calcium/invasion gradient. We identified patterns of life-history traits and genetic differentiation across the habitats that are consistent with local adaptation to low-calcium concentrations in refuge populations and to round goby predation in invaded populations. We also detected restricted gene flow from the low-calcium refugia towards high-calcium invaded populations, implying that the potential for demographic and genetic rescue is limited by natural dispersal. Our study highlights the importance of considering the potentially conflicting effects of local adaptation and gene flow for the resilience of populations coping with invasive predators.

Strongly deleterious mutations influence reproductive output and longevity in an endangered population

Inbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss of function genotypes (LoFs), which are predicted to exert a strong effect on fitness, generally have lower lifetime reproductive success and live shorter lives compared with individuals with lower proportion of LoFs. We also find that juvenile survival is negatively associated with the proportion of homozygous missense genotypes and positively associated with genome wide heterozygosity. Our results demonstrate that homozygosity of strongly and moderately deleterious mutations can be an important cause of trait specific inbreeding depression in wild populations, and mark an important step towards making more informed decisions using applied conservation genetics.

Genetic differentiation and diversity do not explain variation in heterosis or inbreeding depression: empirical evidence from a long-lived iteroparous plant

AbstractAssisted gene flow can restore genetic diversity when genetic drift has driven deleterious alleles to high frequencies in small, isolated populations. Previous crosses among 20 populations of Gymnadenia conopsea documented the strongest heterosis and the weakest inbreeding depression in sparse and small populations, consistent with fixation of mildly deleterious alleles by genetic drift. We genotyped the populations used for crosses, and used 1200–1728 SNPs to test the following predictions: (1) heterosis increases with genetic differentiation (FST) to donor populations and decreases with genetic diversity in the recipient population, (2) inbreeding depression increases with genetic diversity, and (3) genetic diversity increases, and mean FST to other populations decreases, with population size and density. Pairwise FST ranged from very low to moderate (0.005–0.20) and genetic diversity varied moderately among populations (proportion of polymorphic loci = 0.52–0.75). However, neither FST between populations, nor genetic diversity in the recipient population, were related to the strength of heterosis. There was also no association between genetic diversity and the strength of inbreeding depression. Genetic diversity increased and mean FST decreased with population size, consistent with reduced diversity and increased differentiation of small populations by genetic drift. The results indicate that the loci conferring heterosis are not mirrored by overall population differentiation, and limited additional information on potential source populations for genetic rescue is gained by the genetic data. Instead, the use of controlled crosses can directly reveal positive effects of introducing new genetic material, and is a simple method with high potential in conservation.

Genetic rescue often leads to higher fitness as a result of increased heterozygosity across animal taxa.

Biodiversity loss has reached critical levels partly due to anthropogenic habitat loss and degradation. These landscape changes are damaging as they can fragment species distributions into small, isolated populations, resulting in limited gene flow, population declines and reduced adaptive potential. Genetic rescue, the translocation of individuals to increase genetic diversity and ultimately fitness, has produced promising results for fragmented populations but remains underutilized due to a lack of long-term data and monitoring. To promote a better understanding of genetic rescue and its potential risks and benefits over the short-term, we reviewed and analysed published genetic rescue attempts to identify whether genetic diversity increases following translocation, and if this change is associated with increased fitness. Our review identified 19 studies that provided genetic and fitness data from before and after the translocation; the majority of these were on mammals, and included experimental, natural and conservation-motivated translocations. Using a Bayesian meta-analytical approach, we found that on average, genetic diversity and fitness increased in populations post translocations, although there were some exceptions to this trend. Overall, genetic diversity was a positive predictor of population fitness, and in some cases this relationship extended three generations post-rescue. These data suggest a single translocation can have lasting fitness benefits, and support translocation as another tool to facilitate conservation success. Given the limited number of studies with long-term data, we echo the need for genetic monitoring of populations post-translocation to understand whether genetic rescue can also limit the loss of adaptive potential in the long-term.

Whole Genomes Inform Genetic Rescue Strategy for Montane Red Foxes in North America.

A few iconic examples have proven the value of facilitated gene flow for counteracting inbreeding depression and staving off extinction; yet, the practice is often not implemented for fear of causing outbreeding depression. Using genomic sequencing, climatic niche modeling, and demographic reconstruction, we sought to assess the risks and benefits of using translocations as a tool for recovery of endangered montane red fox (Vulpes vulpes) populations in the western United States. We demonstrated elevated inbreeding and homozygosity of deleterious alleles across all populations, but especially those isolated in the Cascade and Sierra Nevada ranges. Consequently, translocations would be expected to increase population growth by masking deleterious recessive alleles. Demographic reconstructions further indicated shallow divergences of less than a few thousand years among montane populations, suggesting low risk of outbreeding depression. These genomic-guided findings set the stage for future management, the documentation of which will provide a roadmap for recovery of other data-deficient taxa.

On the edge: Conservation genomics of the critically endangered dwarf mountain pine Pherosphaera fitzgeraldii

Pherosphaera fitzgeraldii, the Dwarf Mountain Pine, is a critically endangered conifer restricted to cliff ledges within waterfall spray zones in the Greater Blue Mountains Area of New South Wales, Australia. This species is under threat from pollution, invasive weeds, and limited recruitment, which are contributing to its declining population. Using a comprehensive conservation genomic approach, we assessed the population health of P. fitzgeraldii and developed strategic recommendations for its management.Genomic analysis of P. fitzgeraldii revealed the presence of two distinct genetic groups despite the limited distribution of the species. This genetic structure aligns with prevailing wind currents, indicating potential restrictions to pollen or seed exchange between subpopulations. Furthermore, limited gene flow was observed even among nearby subpopulations, emphasizing the risk of increased genetic differentiation due to ongoing isolation. Clonality is widespread in some subpopulations, and all subpopulations displayed signs of inbreeding and genetic depletion despite subdioecy, indicative of historical constraints on gene flow and small population sizes.We offer genomic-based recommendations for prioritizing conservation sites, enhancing genetic diversity in ex situ collections, and guiding future management. Further studies to uncover the sex determination mechanism of P. fitzgeraldii could help maintain balanced sex ratios in ex situ collections and support future genetic rescue efforts. This study underscores the value of genomics in informing protection and recovery of unique threatened species.

Large-scale genome sequencing of giant pandas improves the understanding of population structure and future conservation initiatives

The extinction risk of the giant panda has been demoted from "endangered" to "vulnerable" on the International Union for Conservation of Nature Red List, but its habitat is more fragmented than ever before, resulting in 33 isolated giant panda populations according to the fourth national survey released by the Chinese government. Further comprehensive investigations of the genetic background and in-depth assessments of the conservation status of wild populations are still necessary and urgently needed. Here, we sequenced the genomes of 612 giant pandas with an average depth of ~26× and generated a high-resolution map of genomic variation with more than 20 million variants covering wild individuals from six mountain ranges and captive representatives in China. We identified distinct genetic clusters within the Minshan population by performing a fine-grained genetic structure. The estimation of inbreeding and genetic load associated with historical population dynamics suggested that future conservation efforts should pay special attention to the Qinling and Liangshan populations. Releasing captive individuals with a genetic background similar to the recipient population appears to be an advantageous genetic rescue strategy for recovering the wild giant panda populations, as this approach introduces fewer deleterious mutations into the wild population than mating with differentiated lineages. These findings emphasize the superiority of large-scale population genomics to provide precise guidelines for future conservation of the giant panda.

Patterns of persistence: Genetic and behavioral population complexity of winter flounder amid population declines.

Winter flounder Pseudopleuronectes americanus (Walbaum 1792) are a coastal flatfish species of economic and cultural importance that have dwindled to <15, % of their historic abundance in the southern New England/Mid-Atlantic region of the United States, with evidence indicating near-extirpation of certain local populations. This species exhibits intricate behaviors in spawning and migration that contribute to population complexity and resilience. These behaviors encompass full or partial philopatry to natal estuaries, the generation of multiple pulses of larval delivery, and partial migration. The patterns of genetic diversity within and among estuaries and cohorts presented here carry important implications in understanding the susceptibility to demographic shocks, even if the full extent of genetic diversity within and among winter flounder stocks on the US East Coast remains unresolved. Our findings reveal connectivity between estuaries in Long Island, New York, suggesting the potential for genetic rescue of depleted subpopulations. Family reconstruction and relatedness analysis indicate that split cohorts and migration contingents are not the result of genetically distinct lineages. We found no evidence for genetic structure separating these groups, and in some instances, we were able to detect closely related individuals that belonged to different migratory contingents or cohorts. Characterizing the spatial and behavioral organization of this species at the population level is crucial for comprehending its potential for recovery, not only in terms of biomass but also in reinstating the complex population structure that supports resilience. The search for generality in winter flounder spawning and migration behavior remains elusive, but perhaps the lack of generalities within this species is what has allowed it to persist in the face of decades of environmental and anthropogenic stressors.

Multi-generational benefits of genetic rescue

Genetic rescue—an increase in population fitness following the introduction of new alleles—has been proven to ameliorate inbreeding depression in small, isolated populations, yet is rarely applied as a conservation tool. A lingering question regarding genetic rescue in wildlife conservation is how long beneficial effects persist in admixed populations. Using data collected over 40 years from 1192 endangered Florida panthers (Puma concolor coryi) across nine generations, we show that the experimental genetic rescue implemented in 1995—via the release of eight female pumas from Texas—alleviated morphological, genetic, and demographic correlates of inbreeding depression, subsequently preventing extirpation of the population. We present unequivocal evidence, for the first time in any terrestrial vertebrate, that genetic and phenotypic benefits of genetic rescue remain in this population after five generations of admixture, which helped increase panther abundance (> fivefold) and genetic effective population size (> 20-fold). Additionally, even with extensive admixture, microsatellite allele frequencies in the population continue to support the distinctness of Florida panthers from other North American puma populations, including Texas. Although threats including habitat loss, human-wildlife conflict, and infectious diseases are challenges to many imperiled populations, our results suggest genetic rescue can serve as an effective, multi-generational tool for conservation of small, isolated populations facing extinction from inbreeding.

Airports for the genetic rescue of a former agricultural pest

The intensification of agricultural practices and urbanisation are widespread causes of biodiversity loss. However, the role of artificial habitats in genetic rescue is an aspect that is not well understood. Implementing genetic rescue measures to improve gene flow and maintain a viable population of keystone species is a crucial prerequisite for promoting diverse and resilient ecosystems. Landscape fragmentation and modern agricultural methods have caused the decline and the isolation of the remnant colonies of the endangered European ground squirrel (Spermophilus citellus) throughout its range. However, the artificial habitat, such as airport fields with regular grass mowing, provides suitable conditions for this grassland specialist. We measured home range size and genetic variation of seven souslik colonies in western Slovakia. Based on the 6904 ddRAD SNPs, we found significantly higher individual heterozygosity in colonies on airports compared to colonies on pastures. This indicates a potential for higher fitness of individuals from airport colonies, which can serve as a source for evidence-based translocations. Such an intervention can preserve the genetic diversity of small and isolated populations in the region. We emphasize that conservation management strategies would be strengthened including a specific focus on human-made grassland habitats.

Conserving Evolutionary Potential: Combining Landscape Genomics with Established Methods to Inform Plant Conservation.

Biodiversity conservation requires conserving evolutionary potential-the capacity for wild populations to adapt. Understanding genetic diversity and evolutionary dynamics is critical for informing conservation decisions that enhance adaptability and persistence under environmental change. We review how emerging landscape genomic methods provide plant conservation programs with insights into evolutionary dynamics, including local adaptation and its environmental drivers. Landscape genomic approaches that explore relationships between genomic variation and environments complement rather than replace established population genomic and common garden approaches for assessing adaptive phenotypic variation, population structure, gene flow, and demography. Collectively, these approaches inform conservation actions, including genetic rescue, maladaptation prediction, and assisted gene flow. The greatest on-the-ground impacts from such studies will be realized when conservation practitioners are actively engaged in research and monitoring. Understanding the evolutionary dynamics shaping the genetic diversity of wild plant populations will inform plant conservation decisions that enhance the adaptability and persistence of species in an uncertain future.

Genetic assessment and monitoring of wild, captive, and reintroduced northern leopard frog populations

The northern leopard frog (Lithobates pipiens) has undergone dramatic declines in population size and range over recent decades in western Canada and the United States. In British Columbia, only a single population remains at the Creston Valley Wildlife Management Area. Yet, the continuing viability of this population is uncertain. In this paper, the current genetic structure of northern leopard frog populations in western Canada was assessed using microsatellite markers. Historical samples from the extinct population of Fort Steele in British Columbia were compared with the Creston Valley population to understand changes in population genetic parameters over time. Genotypic data from four populations (Creston Valley, Drain K, Prince Spring, and Cypress Hill) sampled in 2004 and 2019 were compared. To evaluate changes in the genetic diversity of the Creston Valley population over time, allelic richness and expected heterozygosity of the population were compared at three time points using genotypes from 2000, 2004, and 2019. Northern leopard frog populations in western Canada showed high genetic differentiation, with genetic diversity decreasing from east to west. Although there weren’t notable changes in genetic parameters between 2004 and 2019, there was evidence of a decline in diversity between 2000 and 2019. The extinct population of Fort Steele had private alleles, while the current Creston Valley population did not, suggesting a genetic bottleneck in the Creston Valley population. Therefore, genetic rescue, specifically for the endangered Creston Valley population, can be considered as an action to support recovery. Additionally, continued genetic monitoring will help in the effective management of the species by providing information on the success of conservation actions.

Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition

AbstractThe genomics era has facilitated the discovery of new genes that predispose individuals to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ETS-related gene (ERG), a novel, autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor that is critical for definitive hematopoiesis, stem cell function, and platelet maintenance. ERG colocalizes with other transcription factors, including RUNX family transcription factor 1 (RUNX1) and GATA binding protein 2 (GATA2), on promoters or enhancers of genes that orchestrate hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 individuals with thrombocytopenia from 1 family and 14 additional ERG variants in unrelated individuals with BMF/HM, including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germ line ERG variants included cytopenias (thrombocytopenia, neutropenia, and pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense and 1 truncating), including 3 missense population variants, were functionally characterized. Thirteen potentially pathogenic erythroblast transformation specific (ETS) domain missense variants displayed loss-of-function (LOF) characteristics, thereby disrupting transcriptional transactivation, DNA binding, and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture and to promote acute erythroleukemia when transplanted into mice, concordant with these being LOF variants. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germ line ERG variants has clinical implications for patient and family diagnoses, counseling, surveillance, and treatment strategies, including selection of bone marrow donors and cell or gene therapy.

Unveiling the marvels of biodiversity: recent advancements in conservation efforts

This article explores recent advancements in biodiversity conservation, emphasizing the pivotal role of technology in addressing the challenges posed by climate change and the increasing threats to various species. The first section examines technological marvels such as artificial intelligence (AI), remote sensing, and genetic technologies that have revolutionized biodiversity conservation. AI and big data, when integrated, empower scientists to analyze vast datasets efficiently, predict ecological patterns, and recommend effective conservation strategies. AI, remote sensing, and genetic technologies are revolutionizing biodiversity conservation. Examples include AI for wildlife monitoring and species identification, satellite imagery for forest and coral reef health, DNA barcoding and eDNA for species detection, and genetic rescue programs. Integrated approaches combine these technologies for effective habitat and species conservation, improving efficiency and outcomes. Meanwhile, remote sensing technologies, including satellites and drones, offer real-time data on ecosystems, aiding in habitat mapping, species distribution monitoring, and detection of illegal activities. Genetic technologies, like CRISPR-Cas9, hold promise for species resilience, albeit with ethical considerations. In the second section, the article discusses sustainability in conservation efforts, emphasizing the importance of community engagement and the preservation of critical habitats. Collaboration with local communities ensures cultural alignment, while a focus on entire ecosystems, rather than species-specific interventions, maintains biodiversity balance. The third section explores the role of biodiversity in climate change mitigation and as a human life savior. Biodiverse ecosystems act as carbon sinks, contributing to climate change mitigation. Additionally, biodiversity proves to be a valuable source of medicinal compounds and supports global food security by providing diverse crops, livestock, and aquatic species. The article concludes by envisioning a harmonious coexistence between humanity and the diverse species that share our planet. By leveraging technological advancements, engaging local communities, and prioritizing ecosystem preservation, we can strive for a sustainable future where biodiversity flourishes, providing ecological, economic, and cultural richness for generations to come.

Conservation genomics of the critically endangered Chinese pangolin.

The Chinese pangolin (Manis pentadactyla, MP) has been extensively exploited and is now on the brink of extinction, but its population structure, evolutionary history, and adaptive potential are unclear. Here, we analyzed 94 genomes from three subspecies of the Chinese pangolin and identified three distinct genetic clusters (MPA, MPB, and MPC), with MPB further divided into MPB1 and MPB2 subpopulations. The divergence of these populations was driven by past climate change. For MPB2 and MPC, recent human activities have caused dramatic population decline and small population size as well as increased inbreeding, but not decrease in genomic variation and increase in genetic load probably due to strong gene flow; therefore, it is crucial to strengthen in situ habitat management for these two populations. By contrast, although human activities have a milder impact on MPA, it is at high risk of extinction due to long-term contraction and isolation, and genetic rescue is urgently needed. MPB1 exhibited a relatively healthy population status and can potentially serve as a source population. Overall, our findings provide novel insights into the conservation of the Chinese pangolin and biogeography of the mammals of eastern Asia.

When birds of a feather flock together: Severe genomic erosion and the implications for genetic rescue in an endangered island passerine.

The Seychelles magpie-robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation-for-recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re-sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss-of-function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3-fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.

Embracing biodiversity: multispecies population genomics of leafless Bossiaea species shows novel taxa, population dynamics and conservation strategies

Leafless Bossiaea species are a unique group of plants endemic to Australia that present intriguing challenges in taxonomy and conservation because of their morphological simplicity and often small, disjunct populations. We employed whole genome reduced representation sequencing (DArTseq) to enhance our understanding of the population dynamics, diversity and taxonomy of leafless Bossiaea species. Our dataset comprised 52,539 single-nucleotide polymorphisms across 283 samples from 7 leafless Bossiaea species, including 6 listed threatened species. We examined population structure, phylogenetic relationships, kinship and gene flow within and among populations. On the basis of our population-genomic analyses, we propose recognition of the novel taxon Bossiaea vombata subsp. orientalis and a change in status from species (B. milesiae) to subspecies for B. fragrans subsp. milesiae. Additionally, we show extensive clonal reproduction across species and limited gene flow at distances of &gt;1 km, shedding light on the challenges faced by these species. We advocate a coordinated approach to conservation, focusing on restoring self-sustaining populations and leveraging genetic rescue strategies. By addressing the population dynamics of multiple species simultaneously in taxonomically challenging lineages, we can make informed choices to safeguard biodiversity and evolutionary potential.

Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST.

Although effective initially, prolonged androgen deprivation therapy (ADT) promotes neuroendocrine differentiation (NED) and prostate cancer (PCa) progression. It is incompletely understood how ADT transcriptionally induces NE genes in PCa cells. CREB1 and REST are known to positively and negatively regulate neuronal gene expression in the brain, respectively. No direct link between these two master neuronal regulators has been elucidated in the NED of PCa. We show that REST mRNA is downregulated in NEPC cell and mouse models, as well as in patient samples. Phenotypically, REST overexpression increases ADT sensitivity, represses NE genes, inhibits colony formation in culture, and xenograft tumor growth of PCa cells. As expected, ADT downregulates REST in PCa cells in culture and in mouse xenografts. Interestingly, CREB1 signaling represses REST expression. In studying the largely unclear mechanism underlying transcriptional repression of REST by ADT, we found that REST is a direct target of EZH2 epigenetic repression. Finally, genetic rescue experiments demonstrated that ADT induces NED through EZH2's repression of REST, which is enhanced by ADT-activated CREB1 signaling. In summary, our study has revealed a key pathway underlying NE gene upregulation by ADT, as well as established novel relationships between CREB1 and REST, and between EZH2 and REST, which may also have implications in other cancer types and in neurobiology.

Unraveling facets of MECOM-associated syndrome: somatic genetic rescue, clonal hematopoiesis, and phenotype expansion

Unraveling facets of MECOM-associated syndrome: somatic genetic rescue, clonal hematopoiesis, and phenotype expansion