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

Abstract

Optogenetics enables precise regulation of intracellular signaling in target cells. However, the application of optogenetics to induce the differentiation of precursor cells and generate mature cells with specific functions has not yet been fully explored. Here, we focused on osteoclasts, which play an important role in bone remodeling, to develop a novel optogenetics tool, Opto-RANK, which can manipulate intracellular signals involved in osteoclast differentiation and maturation using blue light. We engineered Opto-RANK variants, Opto-RANKc and Opto-RANKm, and generated stable cell lines through retroviral transduction. Differentiation was induced by blue light, and various assays were conducted for functional analysis. Osteoclast precursor cells expressing Opto-RANK differentiated into multinucleated giant cells on light exposure and displayed upregulation of genes normally induced in differentiated osteoclasts. Furthermore, the differentiated cells exhibited bone-resorbing activities, with the possibility of spatial control of the resorption by targeted light illumination. These results suggested that Opto-RANK cells differentiated by light possess the features of osteoclasts, both morphological and functional. Thus, Opto-RANK should be useful for detailed spatiotemporal analysis of intracellular signaling during osteoclast differentiation and the development of new therapies for various bone diseases.

DOI： 10.1038/s41598-024-52056-w

researchmap

Other Link： https://www.nature.com/articles/s41598-024-52056-w

Language：English   Publishing type：Research paper (scientific journal)  

Innate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system. Their biological function and coding mechanisms remain unknown. We show that mouse Fpr3 (Fpr-rs1) recognizes the core peptide motif f-MKKFRW that is predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae. MgrB peptide can be produced and secreted by bacteria, and is selectively recognized by a subset of VSNs. Exposure to the peptide also stimulates VSNs in freely behaving mice and drives innate avoidance. Our data shows that Fpr3 is required for neuronal detection and avoidance of peptides derived from a conserved master virulence regulator of enteric bacteria.

DOI： 10.1038/s41467-019-12842-x

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The mouse vomeronasal organ is specialized in the detection of pheromones. Vomeronasal sensory neurons (VSNs) express chemosensory receptors of two large gene repertoires, V1R and V2R, which encode G-protein-coupled receptors. Phylogenetically, four families of V2R genes can be discerned as follows: A, B, C, and D. VSNs located in the basal layer of the vomeronasal epithelium coordinately coexpress V2R genes from two families: Approximately half of basal VSNs coexpress Vmn2r1 of family C with a single V2R gene of family A8-10, B, or D ('C1 type of V2Rs'), and the other half coexpress Vmn2r2 through Vmn2r7 of family C with a single V2R gene of family A1-6 ('C2 type V2Rs'). The regulatory mechanisms of the coordinated coexpression of V2Rs from two families remain poorly understood. Here, we have generated two mouse strains carrying a knockout mutation in Vmn2r1 by gene targeting in embryonic stem cells. These mutations cause a differential decrease in the numbers of VSNs expressing a given C1 type of V2R. There is no compensatory expression of Vmn2r2 through Vmn2r7. VSN axons coalesce into glomeruli in the appropriate region of the accessory olfactory bulb in the absence of Vmn2r1. Gene expression profiling by NanoString reveals a differential and graded decrease in the expression levels across C1 type of V2Rs. There is no change in the expression levels of C2 type of V2Rs, with two exceptions that we reclassified as C1 type. Thus, there appears to be a fixed probability of gene choice for a given C2 type of V2R.

DOI： 10.1111/ejn.13875

PubMed

researchmap

Language：English   Publisher：(公社)日本生化学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/ncomms9021

Web of Science

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：Japanese  

researchmap

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：KUBAPRO  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：Yodosha  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

researchmap

Event date： 2025.3

Presentation type：Oral presentation (general)  

researchmap

Applicant：国立大学法人東京医科歯科大学

Application no：PCT/JP2012/053705  Date applied：2012.2

Announcement no：WO2012111772 A1  Date announced：2012.8

researchmap