Biology subjects

Poe, D.

Publications and source records attributed to Poe, D..

3 recordsLinked to original sources

bioRxiv2026

Distinct p21 dynamics drive alternative routes to whole-genome duplication through a common CDK4/6-dependent polyploid G0 state

Whole-genome duplication (WGD) fuels tumor evolution and therapy resistance, yet the molecular mechanisms governing the switch from the canonical mitotic cell cycle to the endoreplication cycle remain unclear. Here, we combine single-cell proteomics, manifold learning, and live-cell imaging to map the intersection of the mitotic and endoreplication cycles in breast cancer cells exposed to genotoxic agents. We identify two distinct routes to WGD driven by distinct p21 dynamics. High p21 induction induces G2 exit and endocycling, whereas insufficient p21 permits mitotic entry followed by slippage and endomitosis. This therapy-induced switch acts as a facultative stress response, generating drug-resistant polyploid populations that propagate genomic instability through replication stress and the generation of replication-competent micronuclei. Both paths to WGD converge on a common polyploid G0 state dependent on cyclin D1:CDK4/6 activity to complete the transition to the endoreplication cycle, revealing a shared vulnerability. Sequential treatment with genotoxic agents followed by CDK4/6 inhibitors preserves the cytotoxic efficacy of DNA-damaging drugs while simultaneously blocking entry into the endoreplication cycle and WGD-driven evolutionary rescue. These findings reveal the molecular rules governing the switch from the mitotic to endoreplication cycle and highlight the potential of WGD-blocking drugs as adjuvant therapies to inhibit drug resistance and suppress tumor evolution.

cell biology↗

bioRxiv2025

LivecellX: A Deep-learning-based, Single-Cell Object-Oriented Framework for Quantitative Analysis in Live-Cell Imaging

Live-cell imaging uniquely captures single-cell dynamics in space and time, but robust analysis is limited by segmentation and tracking errors that accumulate across frames. We present LivecellX, a deep-learning-based pipeline that integrates instance-level segmentation error correction with trajectory refinement, leveraging temporal context to recover accurate cell tracks. LivecellX also introduces a benchmark dataset with detailed annotations of common error classes, providing a resource for method development and evaluation. Beyond error correction, the framework incorporates modules for classifying biological processes, reconstructing cell lineages, and analyzing dynamic behaviors. Users can interact with the system programmatically or through a Napari-based graphical interface, enabling flexible integration into diverse workflows. By coupling error-aware correction with comprehensive lineage and dynamics analysis, LivecellX establishes an open, extensible platform that advances the accuracy and scalability of live-cell imaging studies.

biophysics↗

bioRxiv2021

Transiently increased intercommunity regulation characterizes concerted cell phenotypic transition

Phenotype transition takes place in many biological processes such as differentiation and reprogramming. A fundamental question is how cells coordinate switching of expressions of clusters of genes. Through analyzing single cell RNA sequencing data in the framework of transition path theory, we studied how such a genome-wide expression program switching proceeds in five different cell transition processes. For each process we reconstructed a reaction coordinate describing the transition progression, and inferred the gene regulation network (GRN) along the reaction coordinate. In all processes we observed common pattern that the overall effective number and strength of regulation between different communities increase first and then decrease. The change accompanies with similar change of the GRN frustration, defined as overall conflict between the regulation received by genes and their expression states, and GRN heterogeneity. While studies suggest that biological networks are modularized to contain perturbation effects locally, our analyses reveal a general principle that during a cell phenotypic transition, intercommunity interactions increase to concertedly coordinate global gene expression reprogramming, and canalize to specific cell phenotype as Waddington visioned.

systems biology↗