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
  • Zebrafish
  • Brain/blood supply*
  • Lymphatic System/physiopathology
  • Cell Transdifferentiation/physiology*
  • Lymphatic Vessels/physiology
  • Brain Ischemia/physiopathology*
  • Meninges/physiopathology
  • Regeneration/physiology*
  • Stroke/physiopathology
(all 10)
PubMed
34562378 Full text @ Dev. Cell
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
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq10TgTransgenic Insertion
    cq39TgTransgenic Insertion
      cq86TgTransgenic Insertion
        cq87TgTransgenic Insertion
          cq88TgTransgenic Insertion
            cq89TgTransgenic Insertion
              cq90TgTransgenic Insertion
                cq91TgTransgenic Insertion
                  cq101
                    		Indel
                    cq115TgTransgenic Insertion
                      1 - 10 of 16
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      efnb2aCRISPR1-efnb2aCRISPR
                      1 - 1 of 1
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      CFPEFGCFP
                      CreEFGCre
                      Dendra2EFGDendra2
                      DsRedxEFGDsRedx
                      EGFPEFGEGFP
                      GFPEFGGFP
                      NTREFGNTR
                      RFPEFGRFP
                      VenusEFGVenus
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                      Mapping
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                      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.