Biology subjects

McGeever, E.

Publications and source records attributed to McGeever, E..

3 recordsLinked to original sources

bioRxiv2025

Germline stem cell isolation, lineage tracing, and aging in a protochordate

Germline stem cells (GSCs), the source of gametes, are the only stem cells capable of passing genes to future generations and are therefore considered units of natural selection. Yet, the factors that influence GSC fitness, and thus govern GSC competition, which exist in both protochordates and mammals, remain poorly understood. We studied how aging affects GSC fitness in the protochordate Botryllus schlosseri, an evolutionary crosspoint between invertebrates and vertebrates. GSCs were isolated and distinguished from developing and mature gametes using flow cytometry and scRNA-Seq, facilitated by a new PacBio genome assembly. Moreover, their function was validated through a novel lineage tracing approach that combines membrane-labeled GSC transplantation with scRNA-Seq. Leveraging our method to isolate them, single-cell transcriptomics showed significant age-related changes between young and old GSCs. Spermatids and sperm, however, showed minimal changes, suggesting that reproductive aging is governed by GSCs rather than by gametes. Reduced expressions of markers like DDX4 and PIWIL1 in aged GSCs mirrored trends in mammalian datasets, pointing to a conserved GSC-driven aging mechanism across chordate evolution. This study provides new techniques that lay the foundation to investigate further drivers of GSC fitness and highlights fertility-related genes as promising targets for therapies to preserve reproductive health.

cell biology↗

bioRxiv2023

Consensus prediction of cell type labels with popV

Cell-type classification is a crucial step in single-cell analysis. To facilitate this, several methods have been proposed for the task of transferring a cell-type label from an annotated reference atlas to unannotated query data sets. Existing methods for transferring cell-type labels lack proper uncertainty estimation for the resulting annotations, limiting interpretability and usefulness. To address this, we propose popular Vote (popV, https://github.com/YosefLab/popV), an ensemble of prediction models with an ontology-based voting scheme. PopV achieves accurate cell-type labeling and provides effective uncertainty scores. In multiple case studies, popV confidently annotates the majority of cells while highlighting cell populations that are challenging to annotate. This additional step helps to reduce the load of manual inspection, which is often a necessary component of the annotation process, and enables one to focus on the most problematic parts of the annotation, streamlining the overall annotation process.

bioinformatics↗

bioRxiv2023

Zebrahub - Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors

Elucidating the developmental processes of organisms requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate mapping experiments. To demonstrate the versatility of our multi-modal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, Zebrahub, is a foundational resource for studying developmental processes at both transcriptional and spatiotemporal levels, providing researchers with an integrated approach to exploring and analyzing the complexities of cellular lineages during zebrafish embryogenesis.

developmental biology↗