Biology subjects

Mason, F.

Publications and source records attributed to Mason, F..

3 recordsLinked to original sources

bioRxiv2025

β-Catenin Stabilization Protects Against Pulmonary Hemorrhage Through Amphiregulin and BATF- Mediated Regulatory T Cells

Pulmonary hemorrhaging (PH) is a life-threatening condition with a high mortality rate, yet the role of immune cells in its pathogenesis remains poorly defined. Here, we investigated the protective function of {beta}-catenin stabilization in T cells and its impact on PH. Using a novel transgenic mouse model (CAT-Tg) with stabilized {beta}-catenin, we demonstrate that {beta}-catenin stabilization induces a distinct T-cell phenotype characterized by an expansion of central effector memory cells (CD44, CD122, Eomes, T-bet). Mechanistically, this effect was associated with suppression of key proinflammatory pathways, including reduced phosphorylation of STAT1, STAT3, and JAK1. PH was induced using pristane, and CAT-Tg mice were significantly protected from lung damage, showing reduced proteinuria and decreased pulmonary proinflammatory cytokine production compared with wild-type (WT) and T cell-specific {beta}-catenin knockout (cKO) mice. This protection correlated with a marked increase in FOXP3 regulatory T cells (Tregs) in CAT-Tg mice. We further identified a novel mechanism in which {beta}-catenin stabilization enhances lung expression of Amphiregulin and BATF, two molecules essential for Treg function and tissue repair. Adoptive transfer of CAT-Tg Tregs into WT mice with pristane-induced PH conferred superior protection, as evidenced by reduced lung inflammation and proteinuria. The systemic administration of a {beta}-catenin agonist to mice with PH significantly attenuated disease severity. Our bioinformatic analysis confirmed that {beta}-catenin stabilization upregulates pathways associated with tissue repair and immune homeostasis, including PI3K-Akt, angiogenesis, and STAT5 signaling. Collectively, these findings reveal that {beta}-catenin stabilization protects against pulmonary hemorrhage by inducing a specialized T-cell phenotype and establishing a protective Amphiregulin-BATF-Treg axis. This study identifies a novel immunomodulatory pathway with therapeutic potential for PH and other inflammatory lung diseases.

immunology↗

bioRxiv2022

SETD2 safeguards the genome against isochromosome formation

Factors governing the faithful replication of chromosomes are essential for cellular and genomic integrity. While a variety of mechanisms to manage breaks and promote repair of DNA are widely recognized, epigenetic landmarks that preserve telomere-to-telomere replication fidelity and prevent genome instability are not well-understood. SETD2 is the histone methyltransferase responsible for trimethylation on histone H3 lysine 36 and is newly recognized as a tumor suppressor that acts to maintain genome stability. Importantly, SETD2 is frequently lost in cancers that exhibit extensive intratumoral heterogeneity. Here, we demonstrate that loss of SETD2 and H3K36me3 promotes chromosome segregation errors and DNA bridging during mitosis, and that these bridges are driven by the formation of dicentric chromosomes. Cytogenetic analyses revealed that these chromosomes were comprised of mirror-imaged isochromosomes and isodicentric chromosomes that contain two active centromeres. These data demonstrate that the SETD2 histone methyltransferase is essential to prevent a palindromic replication intermediate, whose loss precipitates the formation of a mutable chromatin structure known to initiate a cascade of genomic instability in cancer.

cancer biology↗

bioRxiv2020

Dynamics of altruistic fluid transport in egg development

From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior to fertilization, the nurse cells cytoplasmic contents are transported into the oocyte, which grows as its sister cells regress and die. Although critical for fertility, the biological and physical mechanisms underlying this transport process are poorly understood. Here, we combined live imaging of germline cysts, genetic perturbations, and mathematical modeling to investigate the dynamics and mechanisms that enable directional and complete cytoplasmic transport in Drosophila melanogaster egg chambers. We discovered that during nurse cell (NC) dumping, most cytoplasm is transported into the oocyte independently of changes in myosin-II contractility, with dynamics instead explained by an effective Young-Laplaces law, suggesting hydraulic transport induced by baseline cell surface tension. A minimal flow network model inspired by the famous two-balloon experiment and genetic analysis of a myosin mutant correctly predicts the directionality of transport time scale, as well as its intercellular pattern. Long thought to trigger transport through squeezing, changes in actomyosin contractility are required only once cell volume is reduced by [~]75%, in the form of surface contractile waves that drive NC dumping to completion. Our work thus demonstrates how biological and physical mechanisms cooperate to enable a critical developmental process that, until now, was thought to be a mainly biochemically regulated phenomenon.

developmental biology↗