Biology subjects

Vue, T. Y.

Publications and source records attributed to Vue, T. Y..

5 recordsLinked to original sources

bioRxiv2026

Third Trimester-Equivalent Alcohol Exposure Induces Sex-Dependent Alterations in Locomotor Activity, Anxiety-Risky Behaviors, and Enhances Mechanical Allodynia in Adulthood

Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorders (FASDs), which are neurodevelopmental conditions characterized by behavioral dysregulation, learning deficits, and cognitive inflexibilities. Alcohol exposure is harmful at all stages of human gestation, including the third trimester. This developmental window--characterized by rapid brain growth, myelination, and neural circuit formation--may be particularly vulnerable, yet the long-lasting behavioral and sensory consequences of exposure during this period remain poorly understood. In this study, neonatal mouse pups were exposed to ethanol (EtOH) or air vapor from postnatal day (P) 4 to P8, which is equivalent to a third-trimester alcohol exposure (TTAE) in humans. Blood ethanol concentrations measured at P8 reached approximately 250 mg/dL, consistent with binge-level exposure. Air- and EtOH-exposed mice were then assessed as adults at 5-6 months of age for locomotor activity, anxiety-related risky behaviors, recognition memory, and increased susceptibility to peripheral neuropathy, as indicated by sensitization to light touch following minor chronic constriction injury (mCCI) of the sciatic nerve. We found that TTAE was sufficient to produce long-lasting behavioral outcomes in a sex-dependent manner. Notably, EtOH-exposed males exhibited increased spontaneous locomotor activity and risky behavior, whereas EtOH-exposed females showed minimal or decreased changes compared to their respective controls. However, both EtOH-exposed male and female mice exhibited marked increases in light-touch sensitization, referred to as mechanical allodynia, following mCCI, a response absent in air-exposed controls. Together, these findings reveal that TTAE is highly detrimental to behavioral regulation and creates a vulnerability to developing neuropathic pain in adulthood.

neuroscience↗

bioRxiv2026

ASCL1 and OLIG2 Expression Dynamics Control Glial Cell Fate and Regional Diversity in the Dorsal Forebrain

Gliogenesis is a multistep process that begins with the specification of glial progenitors (GPs) into migrating and proliferating precursor cells, which later differentiate into mature astrocytes and oligodendrocytes. How these developmental processes are coordinated to generate the diverse glial lineages in gray matter (GM) and white matter (WM) in the brain remains poorly understood. Here, we show that the basic-helix-loop-helix (bHLH) transcription factor ASCL1 serves as a direct mechanistic link between glial cell fate specification, migration, proliferation, and differentiation in the dorsal forebrain. Notably, ASCL1 is dynamically expressed in GPs, initiating in the ventricular zone (VZ), peaking in the intermediate zone (IZ), but is downregulated once GPs enter the cortical plate. Lineage tracing of ASCL1+ GPs demonstrates that they subsequently co-express OLIG2 to generate both astrocytes and oligodendrocytes in an "outside-in" pattern starting from the upper cortex inward to the corpus callosum, the opposite pattern of neurogenesis. Gain- and loss-of-function experiments further reveal that a sustained ASCL1 expression is essential for inducing sufficient levels of OLIG2 required to specify oligodendrocyte precursor cell (OPC) fate. Interestingly, a persistent ASCL1 expression also maintains OPCs into postnatal stages by promoting their self-renewal while suppressing their differentiation into postmitotic oligodendrocytes. Together, these findings establish ASCL1 as a key regulator of the spatiotemporal order of glial lineage diversity in cortical GM and callosal WM and implicate ASCL1 dysregulation as an underlying mechanism in the pathogenesis of gliomas.

neuroscience↗

bioRxiv2026

Acute wood smoke exposure is associated with cell-specific hippocampal transcriptomic responses in an accelerated ovarian failure mouse model

BackgroundWildfire events are increasing in frequency and intensity, and it is well-known that aging individuals are more susceptible to air pollution exposures, and that air pollution exposures result in neurological sequelae. Despite this, it is unclear how declining levels of ovarian hormones that naturally occur in aging females influence brain vulnerability to air pollution. Menopause and the menopausal transition represent a period of profound physiological change that affects cardiovascular, neurological, and immune health. MethodsWe tested whether perimenopausal-like hormonal status amplifies hippocampal responses to acute wood smoke (WS) using an ovary-intact, 4-vinylcyclohexene diepoxide (VCD) model of moderate accelerated ovarian failure (AOF) in female C57BL/6 mice. Animals were exposed to HEPA-filtered air (FA) or WS for 4 h/day over 2 consecutive days ([~]0.5 mg/m3). Exposure characterization confirmed a complex mixture of combustion products with significant levels of both trace metals and gas release during WS exposure. ResultsSpatial transcriptomics (10x Visium; (n=4 sections/group) with automated cell-type annotation identified astrocytes, GABAergic and glutamatergic neurons, oligodendrocytes, revealed cell type-specific transcriptional alterations following WS exposure. Distinct transcriptional patterns were observed across all identified neuronal and glial cell populations. ConclusionTogether, these findings define a cell type-resolved transcriptional framework linking WS exposure and ovarian hormone decline and identify potential cellular pathways relevant to hippocampal vulnerability.

pharmacology and toxicology↗

bioRxiv2023

Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM. Subsequently, the dynamic levels and reciprocal binding of ASCL1 and OLIG2 to each other and to downstream target genes then determine the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in defining GSCs by upregulating a collection of ribosomal protein, mitochondrial, neural stem cell (NSC), and cancer metastasis genes - all essential for sustaining the high proliferation, migration, and therapeutic resistance of GSCs.

neuroscience↗

bioRxiv2020

ASCL1 regulates neurodevelopmental transcription factors and cell cycle genes in glioblastoma

Glioblastomas (GBMs) are incurable brain tumors with a high degree of cellular heterogeneity and genetic mutations. Transcription factors that normally regulate neural progenitors and glial development are aberrantly co-expressed in GBM, conferring cancer stem-like properties to drive tumor progression and therapeutic resistance. However, the functional role of individual transcription factors in GBMs in vivo remains elusive. Here, we demonstrate that the basic-helix-loop-helix (bHLH) transcription factor ASCL1 regulates transcriptional targets that are central to GBM development, including neural stem cell and glial transcription factors, oncogenic signaling molecules, chromatin modifying genes, and cell cycle and mitotic genes. We also show that the loss of ASCL1 significantly reduces the proliferation of GBMs induced in the brain of a genetically relevant glioma mouse model, resulting in extended survival times. RNA-seq analysis of mouse GBM tumors reveal that the loss of ASCL1 is associated with downregulation of cell cycle genes, illustrating an important role for ASCL1 in controlling the proliferation of GBM. TABLE OF CONTENTSO_ST_ABSMain PointsC_ST_ABSO_LIASCL1 is co-expressed with neural stem cell/glial transcription factors in GBM C_LIO_LIASCL1 binds to genes that are important for cell proliferation and cancer in the brain. C_LIO_LILoss of ASCL1 downregulates cell cycle genes and increase survival of glioma mouse model. C_LI Table of Content Image O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/958132v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@8aa2d7org.highwire.dtl.DTLVardef@1c908edorg.highwire.dtl.DTLVardef@1690085org.highwire.dtl.DTLVardef@a13728_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗