Genshiro A. Sunagawa

RIKEN Center for Biosystems Dynamics Research · Laboratory for Hibernation Biology

Objectives Acute kidney injury (AKI) is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (Q neurons–induced hypometabolism; QIH). Here, we investigated the efficacy of QIH...

Hibernating mammals actively lower their body temperature to reduce energy expenditure when facing food scarcity¹. This ability to induce a hypometabolic state has evoked great interest owing to its potential medical benefits2,3. Here we show that a hypothalamic neuronal circuit in rodents induces a long-lasting hypothermic and hypometabolic state...

Some mammals enter a hypometabolic state either daily torpor (minutes to hours in length) or hibernation (days to weeks), when reducing metabolism would benefit survival. Hibernators demonstrate deep torpor by reducing both the sensitivity (H) and the theoretical set-point temperature (T R) of the thermogenesis system, resulting in extreme hypother...

The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gen...

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 retina...

Mice enter an active hypometabolic state, called daily torpor when they experience a lowered caloric intake under cold ambient temperature. During torpor, the oxygen consumption rate in some animals 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 app...

Induced differentiation is one of the most experience- and skill-dependent processes in regenerative medicine, and establishing optimal conditions often takes years (an inordinate amount of time). Here, we developed a robotic-AI system that autonomously induces the differentiation of iPS cell-derived RPE (iPSC-RPE) cells. The system performed 216 f...

Mice enter an active hypometabolic state, called daily torpor, when they experience a lowered caloric intake under cool ambient temperature ( T A ). During torpor, the oxygen consumption rate ( VO 2 ) 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 a...

Sleep regulation involves interdependent signaling among specialized neurons in distributed brain regions. Although acetylcholine promotes wakefulness and rapid eye movement (REM) sleep, it is unclear whether the cholinergic pathway is essential (i.e., absolutely required) for REM sleep because of redundancy from neural circuits to molecules. First...

Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also tran...

Document S1. Supplemental Experimental Procedures, Figures S1–S5, Tables S1–S4, and Data S1

This is a correction of some description in Introduction of our original article

Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have los...

Data S2. Table of Manually Annotated Clusters with the Cluster Identifier, Related to Figure 5

Data S3. Source Code to Train the Deep-Learning Model for Clustering the Light, Related to Figure 5

Movie S1. A Mouse with a Retinal Transplant during an SAS Test, Related to Figure 3

Movie S2. A Mouse with a Retinal Transplant during an SAS Test, Related to Figure 3

Data S1. Raster Plot of Light Responses with Manually Annotated Clusters, Related to Figure 5

Full-field electroretinograms (ERGs) are used to objectively assess the mass function of the retina, whereas focal ERGs are used to evaluate the focal retinal function. The purpose of this study was to determine the usefulness of a multiple electrode array (MEA) system for recording ex vivo micro ERGs (mERGs) together with multiunit spike responses...

The changes in the (P1-N1) amplitude during the VPA administration period and the cessation period. Notes: Scatter plots showing changes in retinal sensitivities during the VPA administration period (from baseline to 6 months; n=21) (A) and the cessation period (from 6 months to 12 months; n=9) (B). Multifocal ERGs of the central 20° were measured...

The changes in the retinal sensitivity during the VPA administration period and the cessation period. Notes: Scatter plots show changes in retinal sensitivity during the VPA administration period (from baseline to 6 months; n=24) (A) and the cessation period (from 6 months to 12 months; n=24) (B). Retinal sensitivities of the central 2° were measur...

Purpose The purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP). Patients and methods This was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum a...

The detailed molecular mechanisms underlying the regulation of sleep duration in mammals are still elusive. To address this challenge, we constructed a simple computational model, which recapitulates the electrophysiological characteristics of the slow-wave sleep and awake states. Comprehensive bifurcation analysis predicted that a Ca(2+)-dependent...

Identifying the stages of sleep, or sleep staging, is an unavoidable step in sleep research and typically requires visual inspection of electroencephalography (EEG) and electromyography (EMG) data. Currently, scoring is slow, biased and prone to error by humans and thus is the most important bottleneck for large-scale sleep research in animals. We...

Chronic light can control the amount of locomotor activity of mice both in wild-type and in arrhythmic mice. This could be a candidate to regulate sleep homeostasis. CB57BL/6J mice and two arrhythmic strains, Cry1-/-,Cry2-/- mice and Bmal1-/- mice were used in this study. Shifting mice from constant darkness to constant light showed stable suppress...

ATP-sensitive potassium channels (K+ATP) prominently contribute to basal coronary tone; however, flow reserve during exercise remains unchanged despite channel blockade with glibenclamide (GLI). We hypothesized that increasing perfusion pulsatility, as accompanies exercise, offsets vasoconstriction from K+ATP-channel blockade, and that this effect...

Although treadmill exercise involves a more familiar range of motions and is thus more physiological in terms of daily activity than cycle ergometer exercise, difficulties in controlling the exercise intensity have limited its utility. As heart rate (HR) has been used as a measure of exercise intensity, controlling HR should allow for the proper co...

1. Coronary flow elevation from enhanced perfusion pulsatility is synergistically amplified by adenosine. This study determined the specificity of this interaction and its potential mechanisms. 2. Mean and phasic coronary flow responses to increasing pulsatile perfusion were assessed in anaesthetized dogs, with the anterior descending coronary arte...