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Characterization of the Zebrafish Cell Landscape at Single-Cell Resolution.

ABSTRACT: Zebrafish have been found to be a premier model organism in biological and regeneration research. However, the comprehensive cell compositions and molecular dynamics during tissue regeneration in zebrafish remain poorly understood. Here, we utilized Microwell-seq to analyze more than 250,000 single cells covering major zebrafish cell types and constructed a systematic zebrafish cell landscape. We revealed single-cell compositions for 18 zebrafish tissue types covering both embryo and adult stages. Single-cell mapping of caudal fin regeneration revealed a unique characteristic of blastema population and key genetic regulation involved in zebrafish tissue repair. Overall, our single-cell datasets demonstrate the utility of zebrafish cell landscape resources in various fields of biological research.

SUBMITTER: Jiang M

PROVIDER: S-EPMC8517238 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Characterization of the Zebrafish Cell Landscape at Single-Cell Resolution.

Jiang Mengmeng M Xiao Yanyu Y E Weigao W Ma Lifeng L Wang Jingjing J Chen Haide H Gao Ce C Liao Yuan Y Guo Qile Q Peng Jinrong J Han Xiaoping X Guo Guoji G

Frontiers in cell and developmental biology 20211001

Zebrafish have been found to be a premier model organism in biological and regeneration research. However, the comprehensive cell compositions and molecular dynamics during tissue regeneration in zebrafish remain poorly understood. Here, we utilized Microwell-seq to analyze more than 250,000 single cells covering major zebrafish cell types and constructed a systematic zebrafish cell landscape. We revealed single-cell compositions for 18 zebrafish tissue types covering both embryo and adult stage ...[more]

PMID: 34660600

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Project description:Key Points • A heme rheostat regulates normal erythropoiesis as well as the ineffective erythropoiesis of DBA and MDS-5q.• Marrow cells from patients with MDS-5q with or without the deletion of 5q share transcription profiles. Visual Abstract Abstract The anemias of myelodysplastic syndrome (MDS) and Diamond Blackfan anemia (DBA) are generally macrocytic and always reflect ineffective erythropoiesis yet result from diverse genetic mutations. To delineate shared mechanisms that lead to cell death, we studied the fate of single erythroid marrow cells from individuals with DBA or MDS-5q. We defined an unhealthy (vs healthy) differentiation trajectory using transcriptional pseudotime and cell surface proteins. The pseudotime trajectories diverge immediately after cells upregulate transferrin receptor (CD71), import iron, and initiate heme synthesis, although cell death occurs much later. Cells destined to die express high levels of heme-responsive genes, including ribosomal protein and globin genes, whereas surviving cells downregulate heme synthesis and upregulate DNA damage response, hypoxia, and HIF1 pathways. Surprisingly, 24% ± 12% of cells from control subjects follow the unhealthy trajectory, implying that heme might serve as a rheostat directing cells to live or die. When heme synthesis was inhibited with succinylacetone, more DBA cells followed the healthy trajectory and survived. We also noted high numbers of messages with retained introns that increased as erythroid cells matured, confirmed the rapid cycling of colony forming unit–erythroid, and demonstrated that cell cycle timing is an invariant property of differentiation stage. Including unspliced RNA in pseudotime determinations allowed us to reliably align independent data sets and accurately query stage-specific transcriptomic changes. MDS-5q (unlike DBA) results from somatic mutation, so many normal (unmutated) erythroid cells persist. By independently tracking erythroid differentiation of cells with and without chromosome 5q deletions, we gained insight into why 5q+ cells cannot expand to prevent anemia.

Dataset Information

Characterization of the Zebrafish Cell Landscape at Single-Cell Resolution.

Publications

Characterization of the Zebrafish Cell Landscape at Single-Cell Resolution.

Similar Datasets

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