Biology subjects

Yamagata, M.

Publications and source records attributed to Yamagata, M..

4 recordsLinked to original sources

bioRxiv2023

The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy

Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human iPS cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM. digestThis study investigated the link between Mfn2 and Notch signaling in skeletal muscle atrophy. We used a microgravity system to induce muscle atrophy and found that the loss of Mfn2 leads to decreased numbers of MAM and activation of Notch signaling and that treating MFN2-deficient human iPS cells with a gamma-secretase inhibitor DAPT improved their mitochondrial morphology and function. Additionally, Mfn2-deficient muscle stem cells in mice have a lower capacity to regenerate dystrophic muscles and DAPT treatment improves the regeneration of these cells. The study suggests that targeting the Notch signaling pathway with a gamma-secretase inhibitor could be a therapeutic option for skeletal muscle atrophy caused by defects in Mfn2.

developmental biology↗

bioRxiv2020

CELL ATLAS OF THE CHICK RETINA: SINGLE CELL PROFILING IDENTIFIES 136 CELL TYPES

Retinal structure and function have been studied in many vertebrate orders, but molecular characterization has been largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) to generate a cell atlas of the chick retina. From [~]40,000 single cell transcriptomes, we identified 136 cell types distributed among the six classes conserved across vertebrates - photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and glial cells. To match molecular profiles to morphology, we adapted a method for CRISPR-based integration of reporters into selectively expressed genes. For Muller glia, we found that transcriptionally distinct cells were regionally localized along the anterior-posterior, dorsal-ventral and central-peripheral retinal axes. We also identified immature photoreceptor, horizontal cell and oligodendrocyte types that persist into late embryonic stages. Finally, we analyzed relationships among chick, mouse and primate retinal cell classes and types. Taken together, our results provide a foundation for anatomical, physiological, evolutionary, and developmental studies of the avian visual system.

neuroscience↗

bioRxiv2018

Wide-area all-optical neurophysiology in acute brain slices

Optical tools for simultaneous perturbation and measurement of neural activity open the possibility of mapping neural function over wide areas of brain tissue. However, spectral overlap of actuators and reporters presents a challenge for their simultaneous use, and optical scattering and out-of-focus fluorescence in tissue degrade resolution. To minimize optical crosstalk, we combined an optimized variant (eTsChR) of the most blue-shifted channelrhodopsin reported to-date with a nuclear-localized red-shifted Ca2+ indicator, H2B-jRGECO1a. To perform wide-area optically sectioned imaging in tissue, we designed a structured illumination technique that uses Hadamard matrices to encode spatial information. By combining these molecular and optical approaches we made wide-area maps, spanning cortex and striatum, of the effects of antiepileptic drugs on neural excitability and on the effects of AMPA and NMDA receptor blockers on functional connectivity. Together, these tools provide a powerful capability for wide-area mapping of neuronal excitability and functional connectivity in acute brain slices.

neuroscience↗

bioRxiv2017

RANbodies: reporter-nanobody fusions as versatile, small, sensitive immunohistochemical reagents

Sensitive and specific antibodies are essential for detecting molecules in cells and tissues. However, currently used polyclonal and monoclonal antibodies are often less sensitive than desired, difficult to produce, and available in limited quantities. A promising recent approach to circumvent these limitations is to employ chemically-defined antigen-combining sites called nanobodies, derived from single chain camelid antibodies. Here, we used nanobodies to prepare sensitive unimolecular detection reagents by genetically fusing cDNAs encoding nanobodies to enzymatic or antigenic reporters. We call these fusions between a reporter and a nanobody RANbodies. They can be used to localize epitopes and to amplify signals from fluorescent proteins. They be generated and purified simply and in unlimited amounts, and can be preserved safely and inexpensively in the form of DNA or digital sequence.

neuroscience↗