Biology subjects

Furusho, M.

Publications and source records attributed to Furusho, M..

3 recordsLinked to original sources

bioRxiv2026

Single Nucleus Profiling Reveals Rewired Tumor-Immune-Stromal Cell Communication in Plasmacytoid Urothelial Carcinoma

Plasmacytoid urothelial carcinoma (PUC) is an aggressive histologic subtype of bladder cancer associated with worse patient outcomes and therapeutic response compared to conventional urothelial carcinoma (CUC). While recent work has demonstrated metastatic lymph nodes from PUC tumors have an inflamed phenotype, how the tumor microenvironment (TME) and crosstalk between tumor, stromal, and immune cells in primary PUC bladder tumors differs from those in CUC remains poorly understood. The impact of these differences on response to immunotherapy is also unknown. To understand TME differences between CUC and PUC and their impact on cell signaling, we performed single nucleus RNA sequencing on PUC and CUC tumors, as well as Xenium spatial transcriptomics on a mixed CUC / PUC tumor. We identified increased signaling between PUC-enriched, CDH1-low urothelial cells, immunosuppressive lipid-associated macrophages, and SFRP2+/CTHRC1+ fibroblasts in PUC tumors compared to CUC. Spatial transcriptomics identified increased macrophage infiltration in PUC histology and colocalization of PUC tumor cells, immunosuppressive macrophages, and SFRP2+ fibroblasts. Taken together, this study delineates PUC architecture and demonstrates interplay CDH1-low tumor cells, EMT, and immunosuppressive macrophages, identifying possible therapeutic vulnerabilities in PUC.

cancer biology↗

bioRxiv2026

Region-specific molecular regulatory programs define epithelial identity, progenitor states, and mucus homeostasis in human distal airways

Small distal airways differ from proximal large airways in structure, airflow dynamics, and epithelial composition, and represent a central site of muco-obstructive lung disease pathogenesis. However, due in part to their inaccessibility, the molecular mechanisms that establish regional epithelial identity and govern mucociliary defense in distal airway epithelia remain poorly defined. Here, we integrate transcriptomic, secretomic, and chromatin accessibility analyses of matched primary human large and small airway epithelial cultures to define region-specific regulatory networks. We identify distal airway-specific transcriptional and chromatin programs required for maintaining epithelial identity and mucus homeostasis. Loss of NKX2-1 impairs distal airway secretory cell (DASC) differentiation and shifts mucus properties toward a disease-associated state. Lineage-resolved organoid assays identify an NKX2-1-high distal airway basal cell population with hybrid basal-secretory features as a selective progenitor for DASCs. Collectively, these findings establish a molecular framework for distal airway epithelial biology and define mechanisms regulating region-specific mucociliary host defense.

Cell Biology↗

bioRxiv2024

Soma-to-germline BMP signal is essential for Drosophila spermiogenesis

In the Drosophila testis, developing germ cells are encapsulated by somatic support cells throughout development. Soma-germline interactions are essential for successful spermiogenesis. However, it is still not fully understood what signaling events take place between the soma and the germline. In this study, we found that a Bone Morphogenetic Protein (BMP) ligand, Glass bottom boat (Gbb), secreted from somatic cyst cells (CCs), signals to differentiating germ cells to maintain proper spermiogenesis. Knockdown of Gbb in CCs or the type I BMP receptor Saxophone (Sax) in germ cells leads to a defect in sperm head bundling and decreased fertility. Our Transmission Electron Microscopy (TEM) analyses revealed that the mutant germ cells have aberrant morphology of mitochondria throughout the stages of spermiogenesis and exhibit a defect in nebenkern formation. Elongating spermatids show uncoupled nuclei and elongating mitochondrial derivatives, suggesting that improper mitochondrial development may cause the sperm bundling defect. Taken together we propose a new role of soma-derived BMP signaling, which is essential for spermiogenesis.

developmental biology↗