Biology subjects

Kin, K.

Publications and source records attributed to Kin, K..

6 recordsLinked to original sources

bioRxiv2026

Comparative genomics reveals signatures of distinct metabolic strategies and gene loss associated with Hydra immortality

Hydra is a freshwater cnidarian genus that provides a unique comparative model for aging research, contrasting the immortal H. vulgaris with the aging-inducible H. oligactis. Here, we report a high-quality, chromosome-level genome assembly of H. vulgaris strain AEP.JNIG. Our assembly is comparable in quality to existing resources, facilitating the analysis of genomic diversity across laboratory strains. Epigenomic profiling revealed that gene-body hypermethylation correlates with transcriptional stability and the suppression of spurious transcription in evolutionary conserved genes, suggesting an epigenetic mechanism for genomic integrity. Furthermore, comparative genomics demonstrated that while Hydra conserves fundamental Hallmarks of Aging pathways, the immortal H. vulgaris paradoxically lacks canonical anti-aging genes (e.g., Klotho, NAMPT) found in the aging-inducible H. oligactis. Instead, H. vulgaris exhibits a distinct metabolic signature related to mitochondrial energy production and NTP synthesis. Collectively, our comparative genomics results suggest multiple potential mechanisms associated with the H. vulgaris immortality and the aging traits of H. oligactis, providing novel targets for future functional studies. Significance statementWhy do some organisms age while others appear not to? The freshwater animal Hydra provides a unique opportunity to investigate this question, as closely related species display contrasting aging phenotypes. We generated a high-quality genome assembly for a new strain of a non-aging species and conducted comparative analyses with related strains and an aging species. Even closely related strains can accumulate substantial genetic divergence over time, and stable DNA modification patterns were associated with consistent gene activity, suggesting a mechanism that may help maintain cellular balance. Surprisingly, several well-known longevity genes are present in the aging species but absent in the non-aging one. This suggests that extended lifespan may not simply depend on possessing more "anti-aging" genes, but instead may reflect differences in how core biological processes are organized. Our study provides new insights into the genetic basis of aging and highlights Hydra as a powerful model for understanding longevity.

genomics↗

bioRxiv2025

A novel model system to address the relevance of aggregation in animal origins

The origin of animals from unicellular ancestors remains a fundamental biological question. Cell aggregation, a widespread eukaryotic behaviour, has been underappreciated as a potential pathway to multicellularity. Here, we establish Capsaspora owczarzaki, a close unicellular relative of animals, as a model system to investigate this process. We demonstrate C. owzarzaki aggregates dynamically deploying key metazoan-related genes such as integrins, tyrosine kinases, and Hippo pathway components. Moreover, we further model mathematically the aggregation process, revealing a threshold-like adhesion response to fetal bovine serum (FBS) and dynamic aggregation kinetics driven by cell-cell adhesion and access to FBS. Our findings suggest that cell aggregation could have played a pivotal role in the evolution of animal multicellularity, providing a context for the origin of genes now crucial for animal development. This work positions Capsaspora as a powerful model system for quantitatively studying the evolutionary transition to multicellularity through cell aggregation.

evolutionary biology↗

bioRxiv2023

Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway

Adolescent stress can be a risk factor for abnormal social behavior in the postpartum period, which critically affects the safety of mothers and children. Nonetheless, the underlying mechanisms remain unclear. Using a newly established mouse model with optogenetics and in vivo calcium imaging, we found that adolescent psychosocial stress, combined with pregnancy and delivery, caused hypofunction of the glutamatergic pathway from the anterior insula to prelimbic cortex (AI-PrL pathway), which altered PrL neuronal activity, and in turn led to abnormal social behavior. Specifically, the AI-PrL pathway played a crucial role during recognizing the novelty of other mice by modulating "stable neurons" in PrL, which were constantly activated or inhibited by novel mice. We also observed that glucocorticoid receptor signaling in the AI-PrL pathway had a causal role in stress-induced postpartum changes. Our findings provide novel and functional insights into a cortico-cortical pathway underlying adolescent stress-induced postpartum social behavioral deficits.

neuroscience↗

bioRxiv2022

Sequence-to-expression approach to identify etiological non-coding DNA variations in P53 and cMYC-driven diseases

Disease risk prediction based on DNA sequence and transcriptional profile can improve disease screening, prevention, and potential therapeutic approaches by revealing contributing genetic factors and altered networks. Despite identifying many disease-associated DNA variants through genome-wide association studies, distinguishing deleterious non-coding DNA variations remains poor for most common diseases. We previously reported that non-coding variations disrupting cis-overlapping motifs (CisOMs) of opposing transcription factors significantly affect enhancer activity. Analyzing publicly available ChIP-seq data for P53 and cMYC in human embryonic stem cells and mouse embryonic cells showed that [~]344-366 genomic regions are co-occupied by P53 and cMYC. We identified, on average, two CisOMs per region, suggesting that co-occupancy is evolutionarily conserved in vertebrates. Therefore, we designed in vitro experiments to uncover the significance of the co-occupancy and competitive binding and inhibition between P53 and cMYC on target gene expression. We found that treating U2OS cells with doxorubicin increased P53 protein level while reducing cMYC level. In contrast, no change in protein levels was observed in Raji cells. ChIP-seq analysis showed that 16-922 genomic regions were co-occupied by P53 and cMYC before and after treatment, and substitutions of cMYC signals by P53 were detected after doxorubicin treatment in U2OS. Around 187 expressed genes near co-occupied regions were altered at mRNA level according to RNA-seq data. We utilized a computational motif-matching approach to determine that changes in predicted P53 binding affinity by DNA variations in CisOMs of co-occupied elements significantly correlate with alterations in reporter gene expression. We performed a similar analysis using SNPs mapped in CisOMs for P53 and cMYC from ChIP-seq data in U2OS and Raji, and expression of target genes from the GTEx portal. We found a significant correlation between change in motif-predicted cMYC binding affinity by SNPs in CisOMs and gene expression. In conclusion, our study suggests a generally applicable approach to filter etiological non-coding variations associated with P53 and cMYC-dependent diseases. Author SummaryMost DNA variants associated with common complex diseases fall outside the protein-coding regions of the genome, making them hard to detect and relate to a function. Although many computational tools are available for prioritizing functional disease risk variants outside the protein-coding regions of the genome, the precision of prediction of these tools is mostly unreliable and hence not close to cancer risk prediction. This study brings to light a novel way to improve prediction accuracy of publicly available tools by integrating the impact of cis-overlapping binding sites of opposing cancer proteins, such as P53 and cMYC, in their analysis to filter out deleterious DNA variants outside the protein-coding regions of the human genome. Using a biology-based statistical approach, DNA variants within cis-overlapping motifs impacting the binding affinity of opposing transcription factors can significantly alter the expression of target genes and regulatory networks. This study brings us closer to developing a generally applicable approach capable of filtering etiological non-coding variations in co-occupied genomic regions of P53 and cMYC family members to improve disease risk assessment.

genetics↗

bioRxiv2022

Is the Naked mole-rat a domestic animal?

The Naked mole-rat (NMR) is becoming a prominent model organism due to its peculiar traits, such as eusociality, extreme longevity, cancer resistance, and reduced pain sensitivity. It belongs to the African mole-rats (AMRs), a family of subterranean rodents that includes solitary, cooperative breeding and eusocial species. We identified and quantified the domestication syndrome (DS) across AMRs, a set of morphological and behavioural traits significantly more common and pronounced among domesticated animals than in their wild counterparts. Surprisingly, the NMR shows apparent DS traits compared to the solitary AMR. We argue that many of the NMR unconventional traits can be a side-effect of self-domestication. Animals can self-domesticate when a reduction of the fear response is naturally selected, such as in islands with no predators, or to improve the groups harmony in cooperative breeding species. We propose that self-domestication was necessary to increase social tolerance during the evolution of cooperative breeding and eusociality among AMRs. Finally, we discuss how the DS traits are neutral or beneficial for the subterranean niche and how the increased social tolerance of self-domesticated species could be a side effect of the physical properties of the soil. Our hypothesis provides a novel avenue to enhance the understanding of the extraordinary biology of the NMR.

evolutionary biology↗

bioRxiv2021

Early life stress-induced vulnerability to postpartum mental disturbance: prolonged dysregulation of the HPA axis and behavior

Stress during childhood and adolescence increases the risk for postpartum depression (PPD). Patients with depression who have experienced adverse life events tend to be treatment refractory. However, the mechanism by which stress during childhood and adolescence are involved in the pathophysiology of PPD remains unclear. We investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and behaviors in the postpartum period through mouse and human studies. We observed that adolescent social isolation caused an aberrantly sustained elevation of glucocorticoids via dysregulation of the HPA axis, leading to long-lasting postpartum behavioral changes in female mice. The postpartum behavioral changes elicited by this adolescent stress were not ameliorated by the medicines currently used for PPD treatment. However, a post-delivery treatment with a glucocorticoid receptor antagonist effectively ameliorated the behavioral changes in mice. We also demonstrated a significant impact of stress during childhood and adolescence on the HPA axis dysregulation and PPD in women. We provide experimental evidence that suggests a mechanism-driven therapeutic strategy (repurposing a GR antagonist) for at least some cases of treatment refractory PPD.

molecular biology↗