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

Lange, Merlin; Granados, Alejandro A; Kumar, Shruthi Vijay; Bragantini, Jordão; Ancheta, Sarah; Santhosh, Sreejith; Borja, Michael; Kobayashi, Hirofumi; McGeever, Aaron; Solak, Ahmet; Yang, Bin; Zhao, Xiang; Liu, Yang; Detweiler, Angela M; Paul, Sheryl; Mekonen, Honey; Lao, Tiger; Banks, Rachel A.; Jacobo, Adrián; Balla, Keir M.; Awayan, Kyle; D’Souza, Samuel; Haase, Robert; Dizeux, Alexandre; Tassy, Olivier; Gómez-Sjöberg, Rafael; Huber, Greg; Serra, Mattia; Neff, Norma; Pisco, Angela Oliveira; Royer, Loïc A.

doi:10.1101/2023.03.06.531398

Cited by 44 publications

(52 citation statements)

References 76 publications

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“…S2B). Interestingly, single-cell RNA-Seq datasets revealed that TLNRD1 expression peaks at 24 h post-fertilization during zebrafish embryo development, where it is principally expressed in the blood vasculature (Zebrahub (Lange et al, 2023)). Similarly, TL-NRD1 is also expressed in the vasculature in human embryos (Fig.…”

Section: Resultsmentioning

confidence: 99%

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

Ball,

Ghimire,

Follain

et al. 2023

Preprint

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We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is primarily expressed in the vasculature in vivo and that its depletion leads to vascular abnormalities in vivo and loss of barrier integrity in cultured endothelial cells. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct, high-affinity interaction with CCM2. Modeling and functional testing of TLNRD1 and CCM2 mutants reveal that their interaction is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the 4-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Notably, a CCM2 pathogenic mutation linked to vascular dementia in patients maps to the interface and disrupts the interaction. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity by controlling TLNRD1 bundling activity.

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Section: Resultsmentioning

confidence: 99%

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

Ball,

Ghimire,

Follain

et al. 2023

Preprint

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“…We sought to further explore the tissue specificity of expression of DEGs at 24 hpf. To this end, we used existing single-cell RNA-seq dataset produced by the Zebrahub partners (Lange et al, 2023) to which we applied a dimensionality reduction approach (Marquez-Galera et al, 2022) to differentiate between cell-type-specific signals in bulk RNA-seq DEGs according to the single-cell RNA-seq data at 24 hpf. This approach allows us to increase the accuracy of the spatial distribution of the DEGs as well as the specificity to developmental stages F I G U R E 4 Paternal starvation does not alter F2 survival but is associated with F2 malformations at 24 hpf.…”

Section: Impact Of Paternal Diet On the F1 Transcriptomementioning

confidence: 99%

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Jimenez‐Gonzalez,

Ansaloni,

Nebendahl

et al. 2024

Molecular Ecology

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Dietary restriction in the form of fasting is a putative key to a healthier and longer life, but these benefits may come at a trade‐off with reproductive fitness and may affect the following generation(s). The potential inter‐ and transgenerational effects of long‐term fasting and starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split‐egg clutch design to explore the male‐specific effects of fasting/starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected increased larval growth rate in F1 offspring from starved males and more malformed embryos at 24 h post‐fertilisation in F2 offspring produced by F1 offspring from starved males. Comparing the transcriptomes of F1 embryos sired by starved and fed fathers revealed robust and reproducible increased expression of muscle composition genes but lower expression of lipid metabolism and lysosome genes in embryos from starved fathers. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal effects on extra‐embryonic tissues which are loaded with maternal factors. We compared the embryo transcriptomes to published adult transcriptome datasets and found comparable repressive effects of starvation on metabolism‐associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring's nutritional state, which was defined by the mother.

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“…These atlases are now instrumental for studying a wide range of tissues, organs, and even whole organisms to reveal the origins of cellular differentiation and functional diversity [Quake 2022, Tabula Sapiens Consortium 2022]. Further combined with spatial and time-series studies, they offer a high-definition window into biological development over space and time [Calderon 2022, Qiu 2023, Packer 2019, Sala 2019, Lange 2023]. However, the growing scale of single-cell atlases often poses daunting analytical challenges [Sikkema 2023, Qiu 2023, Lange 2023].…”

Section: Introductionmentioning

confidence: 99%

StaVia: Spatially and temporally aware cartography with higher order random walks for cell atlases

Stassen,

Kobashi,

Huang

et al. 2024

Preprint

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Single-cell atlases are critical for unraveling the cellular basis of health and disease, yet their sheer diversity and vast data landscape in time and space pose daunting computational challenges pertaining to the delineation of multiple simultaneously emerging lineages, the integration of spatial and temporal information, and the visualization of trajectories across large atlases with enough resolution to observe localized transitions. To tackle this intricacy, we introduce StaVia, a computational framework that synergizes multi-faceted single-cell data—spanning time-series data, spatial gene expression patterns, and directional trends from RNA velocity— with higher-order random walks that leverage the memory of cells’ past states. StaVia fuses this method with a cartographic “Atlas View” that offers intuitive graph visualization, simultaneously capturing the nuanced details of cellular development at single-cell resolution as well as the broader connectivity of cell lineages, avoiding common pitfalls of merged distinct trajectories or missed transitional states seen in existing methods which are all memoryless. Notably, we demonstrate that StaVia unlocks new insights into placode development, radial glia pluripotency during neurulation, and the transitions pivotal to these processes in a large-scale Zebrafish developmental atlas. StaVia also allows spatially aware cartography that captures relationships between cell populations based on their spatial location as well as their gene expressions in a MERFISH dataset - underscoring its potential to dissect complex biological landscapes in both spatial and temporal contexts.

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

Cited by 44 publications

References 76 publications

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

StaVia: Spatially and temporally aware cartography with higher order random walks for cell atlases

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