PUBLICATION
Integrated single-cell transcriptome and comparative genome analysis reveal origin of intermuscular bones in zebrafish
- Authors
- Ye, W., Shi, M., Cheng, Y., Liu, Y., Ren, K., Fang, Y., Younas, W., Zhang, W., Wang, Y., Xia, X.Q.
- ID
- ZDB-PUB-250325-10
- Date
- 2025
- Source
- International journal of biological macromolecules : 142397142397 (Journal)
- Registered Authors
- Xia, Xiao-Qin
- Keywords
- Bmp6, Comparative genome, Fish evolution, Intermuscular bones, Single-cell transcriptome
- MeSH Terms
-
- Zebrafish*/genetics
- Mesenchymal Stem Cells/cytology
- Mesenchymal Stem Cells/metabolism
- Animals
- Bone Morphogenetic Protein 6/genetics
- Bone and Bones*/metabolism
- Gene Expression Profiling
- Zebrafish Proteins/genetics
- Osteoblasts/cytology
- Osteoblasts/metabolism
- Genomics/methods
- Cell Differentiation/genetics
- Transcriptome*
- Genome*
- Single-Cell Analysis*
- PubMed
- 40127795 Full text @ Int. J. Biol. Macromol.
Citation
Ye, W., Shi, M., Cheng, Y., Liu, Y., Ren, K., Fang, Y., Younas, W., Zhang, W., Wang, Y., Xia, X.Q. (2025) Integrated single-cell transcriptome and comparative genome analysis reveal origin of intermuscular bones in zebrafish. International journal of biological macromolecules. :142397142397.
Abstract
The evolutionary process of intermuscular bones (IBs) is complex, the molecular regulatory mechanisms of their development are not clear, and even the genes involved in the evolution and development of IBs are poorly understood. In this study, comparative genomic analysis of four fish species with IBs and eleven fish species without IBs identified 106 genes that are more conservatively evolved in fish species with IBs, but highly variable in fish species without IBs. These genes are mainly involved in swimming behavior and BMP signaling pathways. We performed single-cell transcriptome sequencing of IBs origin tissues in zebrafish before and after IBs formation and found that osteoblasts and mesenchymal stem cells (MSCs) increased significantly after IBs formation. RNA velocity analysis showed that osteoblasts in IBs differentiate from MSCs, and the differentiation trajectory of MSCs into osteoblasts was successfully constructed by pseudo-time analysis. Combined with the results of multi-omics analysis, seven candidate genes associated with IBs development were screened and knocked out in zebrafish. It was found that foxn3 mutation resulted in a delay in IB development, whereas bmp6 mutation resulted in a total loss of IB. By comparing the transcriptome of IBs tissues between bmp6+/+ zebrafish and bmp6-/- zebrafish, we found that bmp6 deletion may inhibit the differentiation of MSCs into osteoblasts while promoting the formation of osteoclasts and ultimately inhibiting the formation of IBs. This study provides new insights into the molecular regulatory mechanisms and evolutionary processes of IB development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping