Biology subjects

Kageyama, Y.

Publications and source records attributed to Kageyama, Y..

4 recordsLinked to original sources

bioRxiv2026

Expanding and Decoding the Chemistry of Phospholipid Headgroup in Eukaryotes

Cellular membranes have diverse phospholipids, chemical differences in whose headgroups impact many biological processes. Phosphatidylcholine is an essential phospholipid for human health, but not universally required for life. The evolutionary mechanisms underlying phospholipid preferences remain poorly understood, due to the difficulty of investigating metabolite structure-activity relationships in a cellular context. Here, we developed a generalizable metabolic-rewiring method to manipulate phospholipid headgroups together and their biological effects. This approach utilizes synthetic media to hijack evolutionarily conserved phosphatidylcholine biosynthesis, leveraging xenobiotics as principal precursors for scalable headgroup transformations. By identifying over 100 artificial headgroups, we expanded the chemical diversity of xenobiotic phospholipids. Unexpectedly, we discovered that subtle headgroup alterations produced distinct mammalian cellular activities. We demonstrated that chemical headgroup modifications differentially elicited structure-dependent effects on phospholipid-protein interactions, calcium dynamics, transcriptomic profiles, and stem cell differentiation. Notably, cross-species comparison revealed that human and yeast cells have different headgroup preferences critical for cell life and death. As proof-of-concept, interactome analysis identified headgroup-sensitive human microproteins vital for mitochondrial respiration, but non-conserved in yeast. These results exemplify the evolutionary diversity of key phospholipid-protein interactions, illustrating why humans depend on phosphatidylcholine. Overall, our findings establish a programmable platform for elucidating and engineering phospholipid-driven cellular functions.

cell biology↗

bioRxiv2021

APOE ε4 allele advances the age-dependent decline of amyloid β clearance in the human cortex

IntroductionOur previous study indicated that the pericapillary clearance of amyloid {beta} (A{beta}) declines with age in APOE 3/3 subjects. Here, we examine whether the APOE {varepsilon}4 allele has an impact on this age-related decline. MethodsWe examined 69 autopsy brains of APOE {varepsilon}3/{varepsilon}4 or APOE {varepsilon}3/{varepsilon}3 individuals (30-65 years) for the immunohistochemical localization of intracellular, extracellular, and pericapillary A{beta} in the cerebral cortex. ResultsIn APOE {varepsilon}3/{varepsilon}4 individuals, the percentage of A{beta} positive pericapillary spaces began to decrease (p=0.030), and the number of extracellular A{beta} particles increased in the early 30s (p=0.0008). Those average values were significantly lower (p<0.0001) and higher (p<0.0001), respectively, compared to APOE {varepsilon}3/{varepsilon}3 individuals. DiscussionOur observations indicate that APOE {varepsilon}4 allele advances by one decade at the onset of age-related decline in A{beta} glymphatic clearance. This finding supports early clinical intervention and stratification by APOE genotype to prevent A{beta} deposition and AD progression.

pathology↗

bioRxiv2018

Diffeomorphic registration with intensity transformation and missing data: Application to 3D digital pathology of Alzheimer’s disease

This paper examines the problem of diffeomorphic image mapping in the presence of differing image intensity profiles and missing data. Our motivation comes from the problem of aligning 3D brain MRI with 100 micron isotropic resolution, to histology sections with 1 micron in plane resolution. Multiple stains, as well as damaged, folded, or missing tissue are common in this situation. We overcome these challenges by introducing two new concepts. Cross modality image matching is achieved by jointly estimating polynomial transformations of the atlas intensity, together with pose and deformation parameters. Missing data is accommodated via a multiple atlas selection procedure where several atlases may be of homogeneous intensity and correspond to \"background\" or \"artifact\". The two concepts are combined within an Expectation Maximization algorithm, where atlas selection posteriors and deformation parameters are updated iteratively, and polynomial coefficients are computed in closed form. We show results for 3D reconstruction of digital pathology and MRI in standard atlas coordinates. In conjunction with convolutional neural networks, we quantify the 3D density distribution of tauopathy throughout the medial temporal lobe of an Alzheimers disease postmortem specimen.\n\nAuthor summaryOur work in Alzheimers disease (AD) is attempting to connect histopathology at autopsy and longitudinal clinical magnetic resonance imaging (MRI), combining the strengths of each modality in a common coordinate system. We are bridging this gap by using post mortem high resolution MRI to reconstruct digital pathology in 3D. This image registration problem is challenging because it combines images from different modalities in the presence of missing tissue and artifacts. We overcome this challenge by developing a new registration technique that simultaneously classifies each pixel as \"good data\" / \"missing tissue\" / \"artifact\", learns a contrast transformation between modalities, and computes deformation parameters. We name this technique \"(D)eformable (R)egistration and (I)ntensity (T)ransformation with (M)issing (D)ata\", pronounced as \"Dr. It, M.D.\". In conjunction with convolutional neural networks, we use this technique to map the three dimensional distribution of tau tangles in the medial temporal lobe of an AD postmortem specimen.

neuroscience↗

bioRxiv2017

Shavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis

To compensate for accumulating damages and cell death, adult homeostasis (e.g., body fluids and secretion) requires organ regeneration, operated by long-lived stem cells. How stem cells can survive throughout the animal life yet remains poorly understood. Here we show that the transcription factor Shavenbaby (Svb, OvoL in vertebrates) is expressed in renal/nephric stem cells (RNSCs) of Drosophila and required for their maintenance during adulthood. As recently shown in embryos, Svb function in adult RNSCs further needs a post-translational processing mediated by Polished rice (Pri) smORF peptides and impairing Svb function leads to RNSC apoptosis. We show that Svb interacts both genetically and physically with Yorkie (YAP/TAZ in vertebrates), a nuclear effector of the Hippo pathway, to activate the expression of the inhibitor of apoptosis DIAP1. These data therefore identify Svb as a novel nuclear effector in the Hippo pathway, critical for the survival of adult somatic stem cells.

developmental biology↗