Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The Vps13a gene encodes a lipid transfer protein called VPS13A, or chorein, associated with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondria–endosomes, and lipid droplets. This protein plays a crucial role in inter-organelle communication and lipid transport. Mutations in the VPS13A gene are implicated in the pathogenesis of chorea-acanthocytosis (ChAc), a rare autosomal recessive neurodegenerative disorder characterized by chorea, orofacial dyskinesias, hyperkinetic movements, seizures, cognitive impairment, and acanthocytosis. Previous mouse models of ChAc have shown variable disease phenotypes depending on the genetic background. In this study, we report the generation of a Vps13a flox allele in a pure C57BL/6N mouse background and the subsequent creation of Vps13a knockout (KO) mice via Cre-recombination. Our Vps13a KO mice exhibited increased reticulocytes but not acanthocytes in peripheral blood smears. Additionally, there were no significant differences in the GFAP- and Iba1-positive cells in the striatum, the basal ganglia of the central nervous system. Interestingly, we observed abnormal spermatogenesis leading to male infertility. These findings indicate that Vps13a KO mice are valuable models for studying male infertility and some hematological aspects of ChAc.

DOI： 10.3390/ijms25147776

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Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.1080/15548627.2024.2360345

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected.

Methods

Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing.

Result

After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system’s role in recovery.

Conclusion

The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.

DOI： 10.1186/s41232-024-00319-4

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Other Link： https://link.springer.com/article/10.1186/s41232-024-00319-4/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/jdv.19357

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria. During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass. However, the known mitochondrial fission factors, dynamin-related proteins Dnm1 in yeasts and DNM1L/Drp1 in mammals, are dispensable for mitophagy. Here, we identify Atg44 as a mitochondrial fission factor that is essential for mitophagy in yeasts, and we therefore term Atg44 and its orthologous proteins mitofissin. In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission. Furthermore, we show that mitofissin directly binds to lipid membranes and brings about lipid membrane fragility to facilitate membrane fission. Taken together, we propose that mitofissin acts directly on lipid membranes to drive mitochondrial fission required for mitophagy.

DOI： 10.1016/j.molcel.2023.04.022

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Language：Japanese   Publisher：The Japanese Society of Microscopy  

The ATUM-SEM system, which can analyze serial sections for electron microscopy in three dimensionally, is one of the SEM imaging procedure, and has been attracting attention recently. Among the various serial EM observation procedures, this system has excellent features, such as high-resolution imaging with a wide range of biological specimens and the possibility to image sections repeatedly. Furthermore, by combining ATUM-SEM system and multibeam SEM imaging technology which irradiates 61 beams in parallel to image the serial sections, the entire images of the EM block can be obtained quickly and with high resolution. The whole system enables us to carry out three-dimensional structural analysis of large biological samples from the level of millimeter resolution to that of nanometer resolution. Recently, the localization of a specific molecule can be clearly visualized on a wide range of sections by analyzing with the multibeam SEM and with the CLEM methods, simultaneously. In this review, we would like to summarize the ATUM-SEM system, and the procedure for large area imaging with multibeam SEM, and also describe the cutting-edge imaging technology of the large area CLEM imaging with multi-beam SEM, designated as LA-CLEM (large-area CLEM).

DOI： 10.11410/kenbikyo.56.3_124

CiNii Article

CiNii Books

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Other Link： https://search.jamas.or.jp/link/ui/2022162912

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Event date： 2024.9

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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