Biology subjects

Joyce, B.

Publications and source records attributed to Joyce, B..

5 recordsLinked to original sources

bioRxiv2025

Generative model for the first cell fate bifurcation inmammalian development

The first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asyn-chronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, key transcription factors of TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate bifurcations in mouse development.

developmental biology↗

bioRxiv2023

A Window into Mammalian Basement Membrane Development: Insights from the mTurq2-Col4a1 Mouse Model

Basement membranes (BMs) are specialized sheets of extracellular matrix that underlie epithelial and endothelial tissues. BMs regulate traffic of cells and molecules between compartments, and participate in signaling, cell migration and organogenesis. The dynamics of mammalian BMs, however, are poorly understood, largely due to a lack of models in which core BM components are endogenously labelled. Here, we describe the mTurquoise2-Col4a1 mouse, in which we fluorescently tag collagen IV, the main component of BMs. Using an innovative Planar-Sagittal live imaging technique to visualize the BM of developing skin, we directly observe BM deformation during hair follicle budding and basal progenitor cell divisions. The BMs inherent pliability enables dividing cells to remain attached to and deform the BM, rather than lose adhesion as generally thought. Using FRAP, we show BM collagen IV is extremely stable, even during periods of rapid epidermal growth. These findings demonstrate the utility of the mTurq2-Col4a1 mouse to shed new light on mammalian BM developmental dynamics.

cell biology↗

bioRxiv2023

CyVerse: Cyberinfrastructure for Open Science

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 110,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in two countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

scientific communication and education↗

bioRxiv2023

A novel ground truth dataset enables robust 3D nuclear instance segmentation in early mouse embryos

For investigations into fate specification and cell rearrangements in time-lapse images of preimplantation embryos, automated 3D instance segmentation of nuclei and subsequent nuclear tracking are invaluable. Often, the images low signal-to-noise ratio and high voxel anisotropy and the nucleis dense packing and variable shapes limit the performance of many segmentation methods, while subsequent tracking of nuclear instances is complicated by low frame rates and sample movements. Supervised machine learning approaches can radically improve segmentation accuracy and enable easier tracking, but they often require large amounts of difficult-to-obtain annotated 3D data. Here we report a novel mouse line expressing near-infrared nuclear reporter H2B-miRFP720. H2B-miRFP720 is the longest wavelength nuclear reporter in mice and can be imaged simultaneously with other reporters with minimal overlap. We then generate a dataset, which we call BlastoSPIM, of 3D microscopy images of H2B-miRFP720-expressing embryos with ground truth for nuclear instance segmentation. Using BlastoSPIM, we benchmark the performance of seven convolutional neural networks and identify Stardist-3D as the most accurate instance segmentation method across preimplantation development. We then construct a complete pipeline for nuclear instance segmentation with our BlastoSPIM-trained Stardist-3D models and lineage tracking from the 8-cell stage to the end of preimplantation development (> 100 nuclei). Finally, we demonstrate BlastoSPIMs usefulness as pre-train data for related problems, both for a different imaging modality and for different model systems. BlastoSPIM, its corresponding Stardist-3D models, and documentation of the full associated analysis pipeline are available at: blastospim.flatironinstitute.org.

developmental biology↗

bioRxiv2021

Mites alight! Sunflower crop area and pollen supplementation enhance honey bee resistance to Varroa destructor

Anthropogenic landscape changes can affect parasite epidemiology in wild and agricultural animals. Honey bees are agricultural animals whose services are threatened by loss of floral resources and by parasites, most notably the invasive mite Varroa destructor. Existing mite control strategies rely heavily on chemical treatments that can adversely affect bees. Alternative, pesticide-free control methods are urgently needed to maintain effective pollination services. Many flowering plants provide nectar and pollen that enhance resistance to parasites in animals. Enrichment of landscapes with antiparasitic floral resources could therefore provide a sustainable means of parasite control in pollinators. Floral rewards of Asteraceae plants have been shown to reduce parasitic infection in diverse bee species, including honey and bumble bees. Here, we tested the effects of sunflower (Helianthus annuus) cropland and pollen supplementation on honey bee resistance to macro- and microparasites. Our results show that each doubling of sunflower crop area is associated with a 28% reduction in mite infestation intensity. Late-summer supplementation of colonies with sunflower pollen reduced mite infestation by 2.75-fold relative to an artificial pollen. Our findings suggest the potential for sunflower plantings or pollen supplements to counteract a main driver of honey bee losses worldwide.

ecology↗