PUBLICATION
Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development
- Authors
- Grimm, L., Mason, E., Yu, H., Dudczig, S., Panara, V., Chen, T., Bower, N.I., Paterson, S., Rondon Galeano, M., Kobayashi, S., Senabouth, A., Lagendijk, A.K., Powell, J., Smith, K.A., Okuda, K.S., Koltowska, K., Hogan, B.M.
- ID
- ZDB-PUB-230314-36
- Date
- 2023
- Source
- The EMBO journal 42(11): e112590 (Journal)
- Registered Authors
- Chen, Tyrone, Dudczig, Stefanie, Kobayashi, Sakurako, Mason, Elizabeth, Okuda, Kazuhide Shaun, Paterson, Scott, Rondon Galeano, Maria Cristina, Smith, Kelly, Yu, Hujun
- Keywords
- Notch1, Prox1, Vegfc single-cell sequencing, lymphangiogenesis, lymphatics
- Datasets
- GEO:GSE188341, GEO:GSE188340, GEO:GSE188342
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cells, Cultured
- Endothelial Cells
- Homeodomain Proteins/genetics
- Lymphangiogenesis/genetics
- Lymphatic Vessels*
- Single-Cell Analysis
- Transcription Factors/genetics
- Tumor Suppressor Proteins/genetics
- Zebrafish*/genetics
- PubMed
- 36912146 Full text @ EMBO J.
Citation
Grimm, L., Mason, E., Yu, H., Dudczig, S., Panara, V., Chen, T., Bower, N.I., Paterson, S., Rondon Galeano, M., Kobayashi, S., Senabouth, A., Lagendijk, A.K., Powell, J., Smith, K.A., Okuda, K.S., Koltowska, K., Hogan, B.M. (2023) Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development. The EMBO journal. 42(11):e112590.
Abstract
During development, the lymphatic vasculature forms as a second network derived chiefly from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is a key step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet the downstream mechanisms remain to be elucidated. We here present a single-cell transcriptomic atlas of lymphangiogenesis in zebrafish, revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single-cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a LEC-VEC fate shift. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new downstream targets and regulatory regions of the genome controlled by Prox1 and presents evidence that Prox1 specifies LEC fate primarily by limiting blood vascular and haematopoietic fate. This extensive single-cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping