Biology subjects

Moriwaki, T.

Publications and source records attributed to Moriwaki, T..

3 recordsLinked to original sources

bioRxiv2026

2'-O-Methylated ncRNA condensates form a recombination center for IgH synapsis

How fibrillarin (FBL), an RNA 2'-O-methyltransferase, regulates antibody diversification remains unclear. This study demonstrated that FBL promotes switch (S)-S DNA synapsis at the IgH locus during class switch recombination (CSR), without affecting DNA cleavage. Both RNA-binding and catalytic activities of FBL were essential for CSR. Moreover, MED19 supported DNA cleavage and synapsis by regulating snoRNAs that guide 2'-O-methylation. Mechanistically, FBL methylated -germline transcripts (-GLTs), cis-acting noncoding RNAs forming nuclear condensates harboring machinery for RNA processing, RNP remodeling, and chromatin dynamics. FBL-mediated 2'-O-methylation governed condensate protein composition. FBL suppression aberrantly enriched nucleolar proteins, including WDR74. Crucially, low WDR74 expression in B cells promoted - and -GLT condensate fusion, thereby enhancing S-S synapsis, CSR, and IgH/c-Myc translocation, potentially contributing to poor myeloma prognosis. Altogether, our findings revealed that RNA 2'-O-methylation dictates GLT condensate composition and fusion dynamics to establish a recombination center, driving genomic DNA synapsis in B cells.

molecular biology↗

bioRxiv2024

Comparative analysis of trans-chromosomic rodent models reveals improved somatic hypermutation and class-switch recombination in rats

Humanized rodent models, especially humanization of genetic/genomic components involved in immunity have significantly advanced our understanding of human immune system. Here, we utilized trans-chromosomic (Tc) technology to generate a TC-mAb rat model that stably harbors a mouse artificial chromosome carrying full-length human immunoglobulin (Ig) heavy and kappa light chain genes (IGHK-NAC) in a rat Ig knockout background. In contrast with TC-mAb mice, serum human IgG concentration was found higher than IgM. Number of lymphocytes was recovered, and B cell population in the spleen was normal. Remarkably, repertoire analysis revealed similarities between the model and human PBMCs; somatic hypermutation and class-switch recombination also more closely resembled humans. Furthermore, immunization resulted in generation of antigen-specific human antibodies. Collectively, our strategy to generate both rat and mouse models through introduction of the identical IGHK-NAC offers unprecedented opportunities to comprehensively evaluate genomic regulation and its outcomes associated with genomic sequences and host-derived protein factors.

bioengineering↗

bioRxiv2022

The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to- mesenchymal-like transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders. One Sentence SummarySpecification of the adrenal cortex occurs in adrenogenic coelomic epithelium independent of gonadogenesis in humans and cynomolgus monkeys

developmental biology↗