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Biology subjects

Sunagawa, G. A.

Publications and source records attributed to Sunagawa, G. A..

5 recordsLinked to original sources

A single-nucleus and spatial transcriptomic atlas of the Syrian hamster preoptic area across hibernation states

Hibernation is an extreme physiological state in certain mammals that is characterized by a reversible reduction in metabolic and thermogenic demands. Although the preoptic area has been implicated in the regulation of hibernation, comprehensive molecular and spatial resources for this brain region in hibernating mammals remain limited. Here, we present an integrated transcriptomic resource of the preoptic area generated using single-nucleus RNA sequencing (snRNA-seq) and Xenium-based spatial transcriptomics in a mammalian hibernator, Syrian hamster. The resource includes cross-species transcriptomic annotations relative to mouse preoptic area datasets, seasonal snRNA-seq datasets obtained under non-hibernating and hibernating conditions, and spatially resolved cell-type annotations generated from Xenium profiling. Together, these datasets provide a reference framework for identifying neuronal populations, examining molecular conservation across species and conditions, and integrating transcriptomic identity with spatial organization.

neuroscience↗

EvoPRAISE: computationally guided directed evolution for rational AAV capsid engineering

Advances in neuroscience and gene therapy would be greatly accelerated by adeno-associated virus (AAV) vectors capable of crossing the blood-brain barrier (BBB). Unfortunately, capsids evolved in mice often fail to function in other species, limiting applications in non-model animals such as hibernators. To overcome this limitation, we developed Evolutionary Optimization combined with APPRAISE (EvoPRAISE), a framework that integrates structure-based peptide-protein affinity prediction with directed evolution to design peptide binders for membrane proteins. Using EvoPRAISE, we designed peptide binders that interact with Ly6E, a BBB-associated membrane protein expressed in the Syrian hamster brain. By inserting these peptides into surface-exposed regions of the AAV9 capsid, we developed AAV capsid variants capable of crossing the BBB following systemic administration in Syrian hamsters. Furthermore, this framework enabled the design of AAV capsids displaying peptide binders targeting the human BBB. This rational approach reduces the need for large-scale animal in vivo selection procedures and facilitates the efficient development of receptor-targeted AAV capsids for both neuroscience studies in non-model species and translational gene delivery to the human brain.

bioengineering↗

Contactless metabolism estimation of small animals using high-frequency millimeter-wave radar

Animals flexibly adapt to internal and external environmental changes by utilizing energy produced from oxygen as fuel. By non-invasively monitoring an animals oxygen consumption, it becomes possible to understand an individuals metabolic state. Calorimeters are known for directly measuring oxygen consumption but come with the issue of high initial costs. Despite the development of non-invasive techniques for measuring vital signs--including respiration rate (RR), heart rate (HR), and body temperature (Tb)--as indicators of metabolism, conventional methods encounter difficulties in estimating oxygen consumption rate (VO2). In this study, we developed a system that estimates the oxygen consumption of small animals using signals obtained from millimeter wave (mm-wave) radar technology processed through machine learning. By identifying frequency bands within the mm-wave signals contributing to VO2, our system is capable of predicting oxygen consumption several minutes in advance. Our system enables contactless, low-cost and multiplexed measurements of oxygen consumption, presenting a significant advancement in the field.

physiology↗

Robotic Search for Optimal Cell Culture in Regenerative Medicine

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. The system performed 216 forty-day cell culture experiments, with a total experimentation time of 8,640 days. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that by the pre-optimized culture in terms of pigmented scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

systems biology↗

Integrative Transcription Start Site Analysis and Physiological Phenotyping Reveal Torpor-Specific Expressions in Mouse Skeletal Muscle

Mice enter an active hypometabolic state, called daily torpor, when they experience a lowered caloric intake under cool ambient temperature (TA). During torpor, the oxygen consumption rate (VO2) drops to less than 30% of the normal rate without harming the body. This safe but severe reduction in metabolism is attractive for various clinical applications; however, the mechanism and molecules involved are unclear. Therefore, here we systematically analyzed the expression landscape of transcription start sites (TSS) in mouse skeletal muscles under various metabolic states to identify torpor-specific transcription patterns. We analyzed the soleus muscles from 38 mice in torpid, non-torpid, and torpor-deprived conditions, and identified 287 torpor-specific promoters. Furthermore, we found that the transcription factor ATF3 was highly expressed during torpor deprivation and that the ATF3-binding motif was enriched in torpor-specific promoters. Our results demonstrate that the mouse torpor has a distinct hereditary genetic background and its peripheral tissues are useful for studying active hypometabolism.

physiology↗