Biology subjects

Yamamoto, D.

Publications and source records attributed to Yamamoto, D..

6 recordsLinked to original sources

bioRxiv2026

Myelin basic protein is an RNA chaperone in microglial nuclear retro-transport

CNS oligodendrocytes generate myelin, an RNA-containing proteolipid substance that enhances axonal transmission. In multiple sclerosis (MS), myelin debris is phagocytosed by microglia (MG), and prior studies have detected myelin-derived mRNA in MG nuclei, suggesting a retrograde transport pathway. We report myelin basic protein (MBP) is a nucleic acid-binding and trafficking protein. We found that retro-transport of myelin RNA into the MG nucleus was phagocytosis and importin-dependent. Transcriptomic and proteomic analyses of MG nuclei revealed enrichment of myelin mRNAs and proteins, with MBP singularly detected in soluble and chromatin-associated fractions. MBP bound mRNA with high affinity (Kd {approx} 0.30 nM) and was sufficient to facilitate MG RNA nuclear import in vitro and in vivo. Functionally, MBP mediated the delivery of small interfering RNAs for targeted knockdown of toll-like receptor 4. These findings indicate MBP as an RNA-binding protein capable of MG nuclear import, providing insight into neuroinflammatory pathology of MS.

neuroscience↗

bioRxiv2025

Intrinsic mechanotransduction during apical constriction licenses lineage competence in pluripotent stem cells

To acquire the capacity for multi-lineage differentiation, pluripotent stem cells must undergo a transition from naive pluripotency to lineage competency. This transition requires epithelialization and changes in nuclear architecture. We sought to determine whether the cell and tissue mechanics intrinsic to epithelialization drive pluripotency progression and subsequent lineage commitment to neuroectodermal fate. We demonstrate that naive mouse embryonic stem cells (mESCs) undergoing early differentiation in vitro recapitulate features of epithelialization in the peri-implantation epiblast, specifically apical constriction. We further demonstrate that cell contractility during apical constriction induces a distinct nuclear mechanoresponse, notably enrichment of emerin at the outer nuclear membrane, nuclear envelope localization of SUN2, and the global loss of H3K9me3 heterochromatin which is compensated by H3K27me3. Importantly, these nuclear phenotypes and subsequent neuroectodermal lineage priming require myosin II-mediated contractility, an intact LINC complex, and emerin. We demonstrate that LINC-dependent mechanotransduction through emerin regulates H3K27me3 occupancy on the key early neuroectodermal transcription factor gene, Sox1, implicating a mechanical switch in chromatin mediation of neuroectodermal lineage competence. These results indicate that epithelialization-induced nuclear mechanotransduction poises a critical lineage gene for subsequent expression. HighlightsO_LIAdherent naive mESCs in vitro recapitulate in utero apical constriction morphogenesis. C_LIO_LIContractility, the LINC complex and emerin are required for neuroectodermal lineage competence. C_LIO_LIContractility and the LINC complex are required for widespread loss of H3K9me3 and gain of H3K27me3 on Sox1 promoter. C_LI

cell biology↗

bioRxiv2025

Conservation and diversification of mating behavior patterns among three sibling species in the Drosophila subobscura species subgroup

Behavioral traits are known to evolve rapidly, often even preceding morphological or physiological changes. However, the genomic and neural bases for such rapid behavioral changes remain to be clarified. Drosophila subobscura is a rare example of a species that performs nuptial gift giving, while the mating behaviors of the other two members of the D. subobscura species subgroup, D. madeirensis and D. guanche, remain largely unstudied. In the present study, we characterize and compare mating behaviors of three sibling species of the D. subobscura species subgroup, with the aim of providing a starting point for investigating the neural mechanisms underlying reproductive behavioral divergence in the D. subobscura subgroup. We find that D. madeirensis males exhibit a rich repertoire of courtship behaviors--very similar to that of D. suboscura--including tapping, midleg swinging, proboscis extension and nuptial gift giving. In contrast, D. guanche males perform only tapping and lack the other premating displays, yet they still copulate successfully. We postulate that female promiscuity has promoted the loss of multiple components of the male courtship repertoire in D. guanche. The relatively recent divergence among these species ([~]1.72 Myr between D. guanche and other two species) suggests that only a few genomic and neural changes underpin the striking differences in mating behavior within the subobscura species subgroup. This system offers a promising platform for uncovering the mechanistic basis of rapid behavioral evolution.

evolutionary biology↗

bioRxiv2024

A chromosome-level genome assembly of Drosophila madeirensis, a fruit fly species endemic to the island of Madeira

Drosophila subobscura is distributed across Europe, the Near East, and the Americas, while its sister species, D. madeirensis, is endemic to the island of Madeira in the Atlantic Ocean. D. subobscura is known for its strict light-dependence in mating and its unique courtship displays, including nuptial gift giving. D. subobscura has also attracted the interest of researchers because of its abundant variations in chromosomal polymorphisms correlated to the latitude and season, which have been used as a tool to track global climate warming. Although D. madeirensis can be an important resource for understanding the evolutionary underpinning of these genetic characteristics of D. subobscura, little work has been done on the biology of this species. Here, we used a HiFi long-read sequencing dataset to produce a de novo genome assembly for D. madeirensis. This assembly comprises a total of 111 contigs spanning 135.5 Mb, and has an N50 of 24.2 Mb and a BUSCO completeness score of 98.6%. Each of the six chromosomes of D. madeirensis consisted of a single contig. Breakpoints of the chromosomal inversions between D. subobscura and D. madeirensis were characterized using this genome assembly, updating some of the previously identified locations.

genomics↗

bioRxiv2022

Generation of functional hepatocytes by forward programming with nuclear receptors

Production of large quantities of hepatocytes remains a major challenge for a number of clinical applications in the biomedical field. Directed differentiation of human pluripotent stem cells (hPSC) into hepatocyte-like cells (HLCs) provides an advantageous solution and a number of protocols have been developed for this purpose. However, these methods usually follow different steps of liver development in vitro which is time consuming and requires complex culture conditions. In addition, HLCs lack the full repertoire of functionalities characterising primary hepatocytes. Here, we explore the interest of forward programming to generate hepatocytes from hPSCs and to bypass these limitations. This approach relies on the overexpression of 3 hepatocyte nuclear factors (HNF1A, HNF6 and FOXA3) in combination with different nuclear receptors expressed in the adult liver using the OPTi-OX platform. Forward programming allows for the rapid production of hepatocytes (FoP-Heps) with functional characteristics using a simplified process. We also uncovered that the overexpression of nuclear receptors such as RORc can enhance specific functionalities of FoP-Heps thereby validating its role in lipid/glucose metabolism. Together, our results show that forward programming could offer a versatile alternative to direct differentiation for generating hepatocytes in vitro.

developmental biology↗

bioRxiv2018

Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages

Baculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequent Plasmodium berghei sporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN- and IFN-{gamma} were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. The in vivo passive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN- neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.

immunology↗