Biology subjects

Tsai, F.-Y.

Publications and source records attributed to Tsai, F.-Y..

3 recordsLinked to original sources

bioRxiv2025

Pluripotent Stem Cell Plasticity is Sculpted by a Slit-Independent Robo Pathway in a Regenerative Animal

Whole-body regeneration requires adult stem cells with high plasticity to differentiate into missing cell types. Planarians possess a unique configuration of organs embedded in a vast pool of pluripotent stem cells. How stem cells integrate positional information with discrete fates remains unknown. Here, we use the planarian pharynx to define the cell fates that depend on the pioneer transcription factor FoxA. We find that Roundabout receptor RoboA suppresses aberrant pharynx cell fates by altering foxA expression, independent of the canonical ligand Slit. An RNAi screen for extracellular proteins identifies Anosmin-1 as a potential partner of RoboA. Perturbing global patterning demonstrates that roboA/anosmin-1 functions locally in the brain. By contrast, altering pharynx fate with foxA knockdown induces head-specific neurons in the pharynx, indicating a latent plasticity of stem cells. Our data links critical extracellular cues with cell fate decisions of highly plastic stem cells, ensuring the fidelity of organ regeneration.

developmental biology↗

bioRxiv2024

Epstein-Barr viral product-containing exosome facilitates LIF-associated immunosuppressive polarization of macrophage in nasopharyngeal carcinoma

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is characterized by a highly infiltrated, yet immunosuppressive, tumor microenvironment (TME) in which tumor-associated macrophages (TAMs) play a central role in tumor progression. In this study, we identified exosome-mediated delivery of the EBV oncoprotein LMP1, which acts via induction of leukemia inhibitory factor (LIF), as a key mechanism driving immunosuppressive macrophage polarization. Immunohistochemistry revealed that, in addition to tumor cells, LIF is primarily expressed by stromal TAMs and correlates with poor prognosis. We demonstrated that LMP1-containing exosomes are internalized by macrophages, leading to NF-{kappa}B-dependent upregulation of LIF and polarization toward an immunosuppressive M2d-like phenotype. These macrophages exhibit impaired anti-tumor activity and promote tumor proliferation and vascular dissemination in a LIF-dependent manner. Single-cell transcriptomic analyses of exosome-treated NPC biopsies revealed transcriptional reprogramming across tumor, myeloid, and lymphoid compartments impacting epithelial-mesenchymal transition (EMT); extracellular matrix (ECM) remodeling in tumor cells; immunosuppressive signaling (e.g., CD163 anti-inflammatory and VEGF signaling in macrophages); and enrichment of immune checkpoints and pathways, including PD-1, TGF{beta}-SMAD, and NF-{kappa}B-associated pathways in T cells. Exosome treatment increased expansion of CCL18+-TAMs and expression of CTLA4 in regulatory T cells and exhausted T cells. Immunohistochemistry further confirmed a positive correlation between expression of LIF and CTLA4 in NPC tumors and an inverse correlation between LIF and GZMB/CD8A. These findings define an exosome-driven LMP1-LIF axis that orchestrates immune suppression in NPC and suggest potential targets for restoring anti-tumor immunity.

cancer biology↗

bioRxiv2024

Transgenesis enables mapping of segmental ganglia in the leech Helobdella austinensis

The analysis of how neural circuits function in individuals and change during evolution is simplified by the existence of neurons identified as homologous within and across species. Invertebrates, including leeches, have been used for these purposes in part because their nervous systems comprise a high proportion of identified neurons, but technical limitations make it challenging to assess the full extent to which assumptions of stereotypy hold true. Here, we introduce Minos plasmid-mediated transgenesis as a tool for introducing transgenes into the embryos of the leech Helobdella austinensis (Spiralia; Lophotrochozoa; Annelida; Clitellata; Hirudinida; Glossiphoniidae). We identified an enhancer driving pan-neuronal expression of markers, including histone2B:mCherry, which allowed us to enumerate neurons in segmental ganglia. Unexpectedly, we find that adult Helobdella ganglia contain fewer and more variable numbers of neurons than in previously examined leech species.

zoology↗