Takahiro Yamada

Keio University · Dept. of Biosciences and Informatics

The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Community-driven and highly interdi...

In assisted reproductive technology (ART), embryos produced by in vitro fertilization (IVF) are graded according to their live birth potential, and high-grade embryos are preferentially transplanted. However, rates of live birth following clinical ART remain low worldwide. Grading is based on the embryo shape at a limited number of stages and does...

In fluctuating environments, many microorganisms acquire phenotypic heterogeneity as a survival tactic to increase the likelihood of survival of the overall population. One example of this interindividual heterogeneity is the diversity of ATP concentration among members of Escherichia coli populations under glucose deprivation. Despite the importan...

The number of patients with heart failure and related deaths is rapidly increasing worldwide, making it a major problem. Cardiac hypertrophy is a crucial preliminary step in heart failure, but its treatment has not yet been fully successful. In this study, we established a system to evaluate cardiomyocyte hypertrophy using a deep learning-based hig...

Active and dynamic migration and deformation of cells are universal research targets in cell biology. The leader cells that develop at the wound edge are required to actively reorganize their structure for migration and deformation. Such active reorganization of cellular morphology possibly affects the temperature inside the cells via biochemical r...

Non-biting midges (Chironomidae) are known to inhabit a wide range of environments, and certain species can tolerate extreme conditions, where the rest of insects cannot survive. In particular, the sleeping chironomid Polypedilum vanderplanki is known for the remarkable ability of its larvae to withstand almost complete desiccation by entering a st...

Integration is indispensable, not only in mathematics, but also in a wide range of other fields. A deep learning method has recently been developed and shown to be capable of integrating mathematical functions that could not previously be integrated on a computer. However, that method treats integration as equivalent to natural language translation...

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 mole...

In systems biology, biological phenomena are often modeled by Ordinary Differential Equations (ODEs) and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for...

Pv11 is an insect cell line established from the midge Polypedilum vanderplanki, whose larval form exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 itself is also capable of anhydrobiosis, which is induced by trehalose treatment. Here we report the successful construction of a genome editing system for Pv11 cells and its appli...

In assisted reproductive technology (ART), embryos produced by in vitro fertilization (IVF) are graded according to their live birth potential, and high-grade embryos are preferentially transplanted. However, the rate of live birth following clinical ART remains low worldwide, suggesting that grading is inaccurate. One explanation is that grading i...

In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published....

The Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of extreme hypometabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated....

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyz...

Integration is indispensable, not only in mathematics, but also in a wide range of other fields. A deep learning method has recently been developed and shown to be capable of integrating mathematical functions that could not previously be integrated on a computer. However, that method treats integration as equivalent to natural language translation...

To correctly understand various phenomena in living organisms, new insights can be obtained not only by relative observation but also by quantitative measurement of physical parameters.

Abstract During embryogenesis, cells repeatedly divide and dynamically change their positions in three-dimensional (3D) space. A robust and accurate algorithm to acquire the 3D positions of the cells would help to reveal the mechanisms of embryogenesis. To acquire quantitative criteria of embryogenesis from time-series 3D microscopic images, image...

Pv11 is an insect cell line established from the midge Polypedilum vanderplanki that exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 has also an anhydrobiotic ability which is induced by trehalose treatment. Here we report the successful construction of the genome editing system for Pv11 cells and its application for identify...

Water is essential for living organisms. Terrestrial organisms are incessantly exposed to the stress of losing water, desiccation stress. Avoiding the mortality caused by desiccation stress, many organisms acquired molecular mechanisms to tolerate desiccation. Larvae of the African midge, Polypedilum vanderplanki, and its embryonic cell line Pv11 t...

Mathematical model simulation is a useful method for understanding the complex behavior of a living system. The construction of mathematical models using comprehensive information is one of the techniques of model construction. Such a comprehensive knowledge-based network tends to become a large-scale network. As a result, the variation of analyses...

Regenerative medicine using neural stem cells (NSCs), which self-renew and have pluripotency, has recently attracted a lot of interest. Much research has focused on the transplantation of differentiated NSCs to damaged tissues for the treatment of various neurodegenerative diseases and spinal cord injuries. However, current approaches for distingui...

XitoSBML is a software tool designed to create an SBML (Systems Biology Markup Language) Level 3 Version 1 document from microscopic cellular images. It is implemented as an ImageJ plug-in and is designed to create spatial models that reflect the three-dimensional cellular geometry. With XitoSBML, users can perform spatial model simulations based o...

Image-based deep learning systems, such as convolutional neural networks (CNNs), have recently been applied to cell classification, producing impressive results; however, application of CNNs has been confined to classification of the current cell state from the image. Here, we focused on cell movement where current and/or past cell shape can influe...

Background: Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms use one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such...

Background: Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms use one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such...

Neuroblastoma is the most common solid tumour of childhood, and it metastasizes to distant organs. However, the mechanism of metastasis, which generally depends on the cell motility of the neuroblastoma, remains unclear. In many solid tumours, it has been reported that shear stress promotes metastasis. Here, we investigated the relationship between...

Abstract The larvae of the African midge, Polypedilum vanderplanki, can enter an ametabolic state called anhydrobiosis to overcome fatal desiccation stress. The Pv11 cell line, derived from P. vanderplanki embryo, shows desiccation tolerance when treated with trehalose before desiccation and resumes proliferation after rehydration. However, the mol...

Fig. S1. Calibration of intensity according to the objective height. (A)Diagram of the z‐calibration experiment. The sample was prepared by overlaying two coverslips. Fluorescent beads adsorbed on the coverslip were observed using a × 100 objective lens. The z‐position of the objective lens, which focused on the beads on the coverslip closest to th...

Fig. S11. Relationship between the angle of the pole‐to‐pole axis and the culturing environment without a Wnt3a concentration gradient. A plot of the angle of the pole‐to‐pole axis without a Wnt3a gradient (∆C) during (A) metaphase and (B) postmetaphase in Fig. 5D. We calculated a virtual concentration gradient when Wnt3a‐CM was injected. (C) Proba...

Table S1. Parameters of mould fabrication.

Fig. S12. All plots of each experimental set for Fig. 6F,G. (A) The biased ratio of the pole‐to‐pole axis to the high Wnt3a concentration side with the addition of Dkk1 in metaphase. (B) The biased ratio of the pole‐to‐pole axis to medium flow direction when Dkk1 was added during metaphase.

Fig. S2. Perfusion time until stable gradient. (A) Confocal fluorescence images of FITC‐dextran in the cell culturing channel (channel no. 1 ∼ 5). ‘0 min’ shows the timing that the perfusion started. (B), (C), and (D) Fluctuation of the concentration gradient at channel no. 1 over time at a flow rate of 10 μL·min−1 from the start of perfusion. Each...

Fig. S8. All plots of each experimental set for Fig. 5D,E. (A) The probability that the orientation of the pole‐to‐pole axis is biased towards the higher concentration side of Wnt3a in each experiment. The value of the axis towards and against 0 degree was counted. Among 6 sets of experiments with metaphase cells in the Wnt gradient, once were less...

Fig. S9. Wnt3a adsorption on collagen. (A)Fluorescent images of collagen‐coated glass and Wnt3a‐adsorbed collagen‐coated glass. The collagen‐coated glass was incubated with either culturing medium only or Wnt3a‐CM. After incubation, Wnt3a adsorption was detected by anti‐Wnt3a antibodies. (B) Quantification of Wnt3a adsorption. The intensity of each...

Fig. S10. All plots of each experimental set for Fig. 6C,D (A) The biased ratio of the pole‐to‐pole axis in metaphase cells exposed to the high Wnt3a‐concentration side in each experiment. The number of concentration gradient ranges was divided into four. (B) The biased ratio of the pole‐to‐pole axis in postmetaphase cells exposed to the high Wnt3a...

Fig. S3. Detailed design of the microfluidic cell culture device. Detailed design of the fluidic layer (left), the culturing layer (middle), and the pneumatic layer (right). The upper panel is a magnification of the rectangular area outlined in red in the culturing layer. The lower panel is the cell culture device made by bonding all layers. All un...

Fig. S4. Blocking nonspecific protein adsorption on the PDMS surface. (A) Microscopic images of adsorbed BSA‐FITC on the straight microchannel. Nonspecific adsorption of BSA‐FITC on the untreated surface (left) and the MPC polymer dissolved in absolute ethanol‐coated surface (middle). The surface coated with MPC polymer dissolved in a mixture of ch...

Fig. S5. Profiling of the concentration gradient. (A)Experimental data of normalised intensity (dots) and fitted curve for the data (dashed line) in channel no. 1, at a flow rate of 2 μL·min−1. The residual sum of squares (RSS) value was 0.1059. Error bars show the standard deviation of the normalised intensity. (B) The RSS value in each channel. (...

Fig. S6. LRP6 T1479 activation during mitosis by Wnt3a treatment. (A) Immunofluorescence staining of LRP6 Tp1479 during mitosis. Scale bar = 10 μm. (B) Quantification of the relative phosphorylation level of LRP6 Tp1479 (Control; n = 45, Wnt3a; n = 46). Mean ± standard deviation of the mean are displayed. A Student t‐test was performed. ***P < 0.00...

Fig. S7. All plots of each experimental set for Fig. 4E,F. (A) LRP6 Tp1479 at metaphase was localised to the higher concentration side of Wnt3a. The probability (a/(a + b), y‐axis) is the value obtained by dividing the number of cells in which LRP6 Tp1479 was localised at the higher concentration side by the total number of cells in each experiment...

Proper determination of the cell division axis is essential during development. Wnt3a is a known regulator of the cell division axis; however, the sensitivity of cells to Wnt3a signalling and its role in determining the cell division axis have not been measured to date. To address this gap, we took ad‐vantage of the asymmetric distribution of outer...

Image-based deep learning systems, such as convolutional neural networks (CNNs), have recently been applied to cell classification, producing impressive results; however, application of CNNs has been confined to classification of the current cell state from the image. Here, we focused on dynamic cell movement where current and/or past cell shape ca...

The larvae of the African midge Polypedilum vanderplanki , can enter an ametabolic state called anhydrobiosis to conquer fatal desiccation stress. The Pv11 cell line was derived from embryos of the midge. Desiccated Pv11 cells pretreated with medium containing trehalose resume proliferation after rehydration. The desiccation tolerance of Pv11 cells...

Multicellular organisms develop from the fertilized eggs through numbers of cell divisions. While the pattern of cell division has specific rules for healthy development, some fluctuations for this pattern are allowable. In order to uncover this robust mechanism of development, the position of cells in each embryo must be analyzed quantitatively. I...