Biology subjects

Ke, E.

Publications and source records attributed to Ke, E..

2 recordsLinked to original sources

bioRxiv2022

Delineate clonal dynamics of ovarian cancer initiating cells during pre-malignant progression using a mouse genetic mosaic system

Different cellular compartments within a tissue present distinct cancer-initiating capacities. Current approaches to delineate cancer-initiating heterogeneity require a well-understood lineage hierarchy and cell-specific genetic tools, which are lacking for many tissues. Here, we circumvented this hurdle and investigated the capacity of fallopian tube cells in initiating serous ovarian cancer, utilizing a mouse genetic system that generates scattered GFP-labeled mutant cells. Through quantitative tracing of clonal expansion of individual mutant cells, we revealed that only a rare primitive subset enriched in the distal fallopian tube is capable of clonal expansion whereas others stall immediately upon acquiring oncogenic mutations. Expanded clones from this subset then encountered further attrition: many stalled shortly after while others sustained small cluster of proliferative cells and biased differentiation toward primitive fate. Taken together, our study showcases quantitative clonal tracing as a powerful approach to investigate cancer-initiating heterogeneity and clonal trajectory in tissues with limited prior knowledge.

cancer biology↗

bioRxiv2021

PML-Dependent Memory of Type I Interferon Treatment Results in a Restricted Form of HSV Latency

Herpes simplex virus (HSV) establishes latent infection in long-lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency is unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also found that the subnuclear condensates, promyelocytic leukemia-nuclear bodies (PML-NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV-1 genomes colocalized with PML-NBs throughout a latent infection of neurons only when type I IFN was present during initial infection. Depletion of PML prior to or following infection did not impact the establishment latency; however, it did rescue the ability of HSV to reactivate from IFN-treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response during de novo infection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.

immunology↗