Biology subjects

Taira, N.

Publications and source records attributed to Taira, N..

3 recordsLinked to original sources

bioRxiv2025

Balanced DNA-to-Cytoplasm Ratio at the 2-Cell Stage Is Critical for Mouse Preimplantation Development

Vertebrate development typically begins with a diploid fertilized egg but can also be initiated parthenogenetically with a haploid maternal genome, though such development fails to reach completion. Among vertebrates, mammalian haploid embryos are particularly prone to arrest during early preimplantation stages for reasons that remain unclear. Here, using mouse embryos with varying cell sizes and genome ploidy, we show that developmental arrest is primarily caused not by haploidy itself but an imbalance between genome ploidy and cytoplasmic volume. Haploid embryos exhibit cytokinesis failure, frequently accompanied by chromosome segregation failure due to malformed spindles beginning at the second mitosis, with about half of the affected blastomeres subsequently arresting before the morula stage. Strikingly, restoring the DNA-to- cytoplasm (D/C) ratio by halving the cytoplasmic volume alleviates these defects. Similarly, diploid embryos with doubled cytoplasmic volume show mitotic and developmental abnormalities resembling those of haploid embryos, whereas tetraploid embryos with the same volume develop normally. These findings demonstrate that a proper D/C ratio, rather than genome ploidy, is critical for mouse embryos to reach the morula stage. Moreover, halving the D/C ratio at later developmental stages, such as the late G2 phase of the 1-cell stage or during the 2-cell stage, progressively improves developmental outcomes. When the D/C ratio is reduced at the end of the 2-cell stage, development proceeds normally. Our findings identify a critical temporal window during which a balanced D/C ratio is essential for mitotic fidelity and successful preimplantation development. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/651589v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@72a664org.highwire.dtl.DTLVardef@10a22c1org.highwire.dtl.DTLVardef@6fbedforg.highwire.dtl.DTLVardef@5c5b1d_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIHalved D/C ratio impairs preimplantation development in mouse embryos C_LIO_LIHalved D/C ratio causes cytokinesis failure from the second mitosis C_LIO_LIDelaying D/C ratio halving to late 2-cell stage alleviates developmental defects C_LI

cell biology↗

bioRxiv2025

Delineating JunB's Crucial Function in Mature Th17 Cells through Inducible Targeted Protein Degradation

The AP-1 transcription factor JunB is essential for the differentiation of pathogenic T helper 17 (Th17) cells, which are key mediators of autoimmune diseases such as multiple sclerosis and colitis. While the importance of JunB during Th17 polarization is known, its role in mature Th17 cells--critical therapeutic targets in these diseases--remains unclear. In this study, we employed the dTAG system, a targeted protein degradation approach, to deplete JunB in Th17 cells generated both in vitro and in vivo. During pathogenic Th17 cell differentiation, JunB degradation replicated known effects of JunB deficiency, including reduced expression of interleukin (IL)-17A and the genes encoding ROR{gamma}t (Rorc) and the IL-23 receptor (Il23r). In contrast, in mature pathogenic Th17 cells, JunB degradation downregulated Il23r without affecting IL-17A or Rorc expression. Furthermore, JunB degradation compromised the viability of mature pathogenic Th17 cells. Transcriptomic analyses revealed that JunB regulates distinct gene sets during Th17 polarization compared to mature Th17 cells. The gene Inhba, which encodes activin A, was identified as a JunB target in both stages. Supplementation with activin A restored IL-17A and Rorc expression during pathogenic Th17 cell differentiation. These findings demonstrate that JunB maintains mature pathogenic Th17 cell phenotypes, including IL-23 receptor expression, and supports pathogenic Th17 cell survival. As IL-23 signaling is crucial for sustaining pathogenic Th17 cells, targeting JunB may offer a therapeutic strategy to limit Th17-driven autoimmune inflammation.

immunology↗

bioRxiv2022

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, factors associated with this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we find that baseline expression of AP-1 transcription factors, FOS and ATF3, is inversely correlated with BNT162b2 mRNA vaccine-induced T-cell responses. FOS expression is associated with transcription modules related to baseline immunity, but it is negatively associated with those related to T-cell activation upon BNT162b2 mRNA stimulation. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with FOS and ATF3 expression and inversely correlated with BNT162b2-induced T-cell responses. Taken together, these results demonstrate that baseline expression of AP-1 genes, which is associated with the gut microbial fucose/rhamnose degradation pathway, is a key negative correlate of BNT162b2-induced T-cell responses.

immunology↗