PUBLICATION
Acute brain vascular regeneration occurs via lymphatic transdifferentiation
- Authors
- Chen, J., Li, X., Ni, R., Chen, Q., Yang, Q., He, J., Luo, L.
- ID
- ZDB-PUB-210926-4
- Date
- 2021
- Source
- Developmental Cell 56(22): 3115-3127.e6 (Journal)
- Registered Authors
- Luo, Lingfei
- Keywords
- none
- MeSH Terms
-
- Animals
- Regeneration/physiology*
- Lymphatic System/physiopathology
- Lymphatic Vessels/physiology
- Stroke/physiopathology
- Zebrafish
- Meninges/physiopathology
- Cell Transdifferentiation/physiology*
- Brain/blood supply*
- Brain Ischemia/physiopathology*
- PubMed
- 34562378 Full text @ Dev. Cell
Citation
Chen, J., Li, X., Ni, R., Chen, Q., Yang, Q., He, J., Luo, L. (2021) Acute brain vascular regeneration occurs via lymphatic transdifferentiation. Developmental Cell. 56(22):3115-3127.e6.
Abstract
Acute ischemic stroke damages the regional brain blood vessel (BV) network. Acute recovery of basic blood flows, which is carried out by the earliest regenerated BVs, are critical to improve clinical outcomes and minimize lethality. Although the late-regenerated BVs form via growing along the meninge-derived ingrown lymphatic vessels (iLVs), mechanisms underlying the early, acute BV regeneration remain elusive. Using zebrafish cerebrovascular injury models, we show that the earliest regenerated BVs come from lymphatic transdifferentiation, a hitherto unappreciated process in vertebrates. Mechanistically, the LV-to-BV transdifferentiation occurs exclusively in the stand-alone iLVs through Notch activation. In the track iLVs adhered by late-regenerated BVs, transdifferentiation never occurs because the BV-expressing EphrinB2a paracellularly activates the iLV-expressing EphB4a to inhibit Notch activation. Suppression of LV-to-BV transdifferentiation blocks acute BV regeneration and becomes lethal. These results demonstrate that acute BV regeneration occurs via lymphatic transdifferentiation, suggesting this process and key regulatory molecules EphrinB2a/EphB4a/Notch as new postischemic therapeutic targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping