PUBLICATION
Proteostasis governs differential temperature sensitivity across embryonic cell types
- Authors
- Dorrity, M.W., Saunders, L.M., Duran, M., Srivatsan, S.R., Barkan, E., Jackson, D.L., Sattler, S.M., Ewing, B., Queitsch, C., Shendure, J., Raible, D.W., Kimelman, D., Trapnell, C.
- ID
- ZDB-PUB-231112-1
- Date
- 2023
- Source
- Cell 186: 50155027.e125015-5027.e12 (Journal)
- Registered Authors
- Kimelman, David, Raible, David
- Keywords
- developmental robustness, single-cell RNA-seq, variability, zebrafish
- Datasets
- GEO:GSE202294
- MeSH Terms
-
- Animals
- Embryonic Development
- Gene Expression Regulation, Developmental
- Proteostasis*
- Temperature
- Zebrafish*/growth & development
- PubMed
- 37949057 Full text @ Cell
Citation
Dorrity, M.W., Saunders, L.M., Duran, M., Srivatsan, S.R., Barkan, E., Jackson, D.L., Sattler, S.M., Ewing, B., Queitsch, C., Shendure, J., Raible, D.W., Kimelman, D., Trapnell, C. (2023) Proteostasis governs differential temperature sensitivity across embryonic cell types. Cell. 186:50155027.e125015-5027.e12.
Abstract
Embryonic development is remarkably robust, but temperature stress can degrade its ability to generate animals with invariant anatomy. Phenotypes associated with environmental stress suggest that some cell types are more sensitive to stress than others, but the basis of this sensitivity is unknown. Here, we characterize hundreds of individual zebrafish embryos under temperature stress using whole-animal single-cell RNA sequencing (RNA-seq) to identify cell types and molecular programs driving phenotypic variability. We find that temperature perturbs the normal proportions and gene expression programs of numerous cell types and also introduces asynchrony in developmental timing. The notochord is particularly sensitive to temperature, which we map to a specialized cell type: sheath cells. These cells accumulate misfolded protein at elevated temperature, leading to a cascading structural failure of the notochord and anatomic defects. Our study demonstrates that whole-animal single-cell RNA-seq can identify mechanisms for developmental robustness and pinpoint cell types that constitute key failure points.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping