2024
mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis
Min W, Qin L, Zhang H, López-Giráldez F, Jiang N, Kim Y, Mohan V, Su M, Murray K, Grutzendler J, Zhou J. mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis. Circulation Research 2024, 135: e94-e113. PMID: 38957991, PMCID: PMC11293987, DOI: 10.1161/circresaha.123.324015.Peer-Reviewed Original ResearchCerebral vascular malformationsEndothelial progenitor cellsBlood-brain barrier integritySingle-cell RNA sequencing analysisDisruption of blood-brain barrier integrityBarrier integrityResident endothelial progenitor cellsRNA sequencing analysisTissue immunofluorescence analysisEndothelial cellsEPC clustersStem cell markersFocal neurological deficitsBrain's neurovascular unitMTOR signalingHuman CCM lesionsMTORC1 signalingBlood-brain barrierCapillary endothelial cellsCCM pathogenesisVascular malformationsLesion signaturesNeurological deficitsCell markersClonal expansion
2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformations