Biology subjects

Nagano, T.

Publications and source records attributed to Nagano, T..

5 recordsLinked to original sources

bioRxiv2026

Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration

The alveolar sac architecture is essential for efficient gas exchange and must be precisely maintained throughout life; however, how this delicate structure is preserved during adult regeneration remains poorly understood. Using a mouse pneumonectomy model, we found that Lgr6+ Hhip+ ductal myofibroblasts, a poorly characterized mesenchymal population, are indispensable for maintaining alveolar integrity during lung regrowth. Comprehensive characterization using single-cell transcriptomics, mouse genetics, and pharmacological assays demonstrated that these ductal myofibroblasts secrete myogenic factors, most notably CCN4, to reactivate a myogenic program that converts them into contractile PA-DMFs, thereby preserving alveolar architecture. Lineage-tracing further revealed that these ductal myofibroblasts originate from embryonic MCAM- SMA+ distal progenitors via subepithelial TGF-{beta} signaling, serving as a lifelong guardian of alveolar structural integrity. Notably, cross-species analysis identified an analogous population of LGR6+ fibromyocytes in human respiratory bronchioles. Together, these findings indicate ductal myofibroblasts as a developmentally programmed cell population that reactivate a contractile program to structurally support the regeneration of adult lungs.

developmental biology↗

bioRxiv2026

Interstitial macrophages drive chronic lung allograft dysfunction

Despite immunosuppressive regimens targeting adaptive immunity, chronic lung allograft dysfunction (CLAD) remains the major obstacle to durable lung allograft survival. Here, we identify colony-stimulating factor 1 receptor (CSF1R)-expressing interstitial macrophages as critical orchestrators of CLAD. Using lung tissue from patients with CLAD and a mouse model of mismatched lung transplantation, we show that both donor-derived tissue-resident and recipient- monocyte-derived interstitial macrophages spatially co-localize within peribronchial immune aggregates in patients with CLAD. These interstitial macrophages express distinct cytokine programs that include those implicated in the recruitment of T and B cells. Pharmacological inhibition of CSF1R after lung transplantation in mice reduced interstitial macrophage abundance and attenuated CLAD pathology. Our findings identify donor- and recipient-derived interstitial macrophages as upstream regulators of CLAD and suggest CSF1R as a therapeutic target for its prevention and treatment.

immunology↗

bioRxiv2026

A genomic and proteomic characterization of mannan-degradable Bacillus sp. TTS1, isolated from Tomakomai Forest in Hokkaido

A challenge in using plant biomass is its highly recalcitrant nature, which makes it economically infeasible to utilize. In natural environments, various microbes, including bacteria and fungi, are reported to decompose plant cell wall materials such as cellulose and hemicellulose, and there may be undescribed microbes that contribute to the degradation of plant biomass. We focused on isolating novel plant biomass-degrading bacteria and screened more than 100 isolates from the Tomakomai experimental forest in Hokkaido, Japan. Among them, one novel Bacillus species was chosen for whole-genome sequencing. Comparative genomics and a carbon source utilization assay indicated that the isolate belongs to a subspecies of Bacillus subtilis, which we named B. sp. TTS1. Glucose, cellobiose, xylose, xylan, mannose, or mannan was used as the sole carbon source in the minimum medium, and the growth of this bacterium was determined. Furthermore, a proteomic analysis of B. sp. TTS1 was performed using culture supernatants from various polysaccharide-containing media. In the present study, several key enzymes involved in plant biomass degradation were identified, namely {beta}-1,4-mannanase and xylanase, and they were highly enriched in all tested polysaccharides.

microbiology↗

bioRxiv2022

High-resolution promoter interaction analysis in Type 3 Innate Lymphoid Cells implicates Batten Disease gene CLN3 in Crohn's Disease aetiology

Innate lymphoid cells (ILCs) are rare, tissue-resident innate lymphocytes that functionally mirror CD4+ T helper cell lineages but lack antigen receptors. Type 3 ILCs (ILC3s) are enriched in the gut, airways, and mucosal lymphoid tissues, where they regulate inflammation and promote barrier integrity. To define the regulatory architecture of primary human ILC3s, we map promoter-anchored chromosomal contacts using high-resolution, low-input Promoter Capture Hi-C (PCHi-C) in these cells alongside CD4+ T cells. By combining statistical detection with a PCHi-C-adapted Activity-by-Contact approach, we link promoters to distal regulatory elements, identifying hundreds of ILC3-specific contacts. We use these maps to connect genome-wide association study (GWAS) risk variants for Crohns disease to target genes using multiCOGS, a Bayesian framework that integrates PCHi-C with summary-statistic imputation and multivariate fine-mapping. This analysis highlights both known and unanticipated candidates, including CLN3, a causal gene for the neurodevelopmental Batten disease. Using a mouse ILC3-like cell line, we show that Cln3 is downregulated upon cytokine stimulation, and Cln3 overexpression alters stimulation-induced transcriptional programmes and cytokine secretion. Extending this approach, we generate a catalogue of ILC3-linked risk genes for five additional autoimmune conditions and show that they are enriched for regulators of the ILC3 inflammatory response identified in a CRISPR interference screen. Together, these findings illuminate long-range gene control in ILC3s and prioritise known and newly implicated autoimmune risk genes with potential roles in this clinically important cell type.

genetics↗

bioRxiv2016

Cell cycle dynamics of chromosomal organisation at single-cell resolution

Chromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.

genomics↗