Zebrahub – a single-embryo single-cell RNA sequencing atlas of zebrafish development

Elucidating the developmental process of an organism will require the complete cartography of cellular lineages in the spatial, temporal, and molecular domains. Researcher at the Chan Zuckerberg Biohub have developed Zebrahub, a comprehensive dynamic atlas of zebrafish embryonic development that combines single-cell sequencing time course data with light-sheet microscopy-based lineage reconstructions. Zebrahub is a foundational resource to study developmental processes at both transcriptional and spatiotemporal levels. It is publicly accessible as a web-based resource, providing an open-access collection of datasets and tools. Using this resource the researchers shed new light on the pluripotency of Neuro-Mesodermal Progenitors (NMPs). They find that NMPs are pluripotent only during early axis elongation before becoming exclusively mesodermal progenitors. They attribute this restriction in NMP cell fate to emerging morphodynamic features that compartmentalize tissue motion.

Zebrahub – Multimodal Zebrafish Developmental Atlas

(a) Zebrahub’s scRNAseq experimental pipeline for single-zebrafish-embryo single-cell RNA sequencing across developmental stages (dpf: day post fertilization, hpf: hours post fertilization). From left to right we show: First, the number of cells per time point and replicate. Second, an example UMAP for a 14 hpf embryo transcriptome colored by cell type (3862 cells total). Third, Zebrahub’s web portal allows the exploration of scRNAseq data online. (b) UMAP representation of the entire dataset of 40 single-embryo transcriptomes colored by developmental stage (120k total cells). (c) Same but colored by annotated cell types. (d) Maximum intensity projections of a 12-hour light-sheet live-imaging of a zebrafish embryo expressing histone-mCherry (cyan) and mezzo-GFP (magenta). Arrows indicate the mezzo-positive cells. (e) Similar imaging but on an embryo expressing the photoconvertible protein Dendra2. Photoconverted cells are in red (blue arrows). (f) Overview of the two light-sheet microscopes used in this study: OpenSiMView –two detections and two illuminations multi-view light-sheet microscope (left), and DaXi – a high-resolution, large field of view and multi-view single-objective light-sheet microscope (right). (g) Computational pipeline for image processing and nuclei tracking applied to images of a histone-mCherry zebrafish embryo acquired with our DaXi microscope (see Methods). (h) Screenshot of the in silico fate mapping napari plugin available as part of Zebrahub

Availabilityhttps://zebrahub.ds.czbiohub.org/transcriptomics

Lange M, Granados A, VijayKumar S et al. (2023) Zebrahub – Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors. bioRXiv [online preprint]. [article]

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