2024
Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions
Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz M. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. The EMBO Journal 2024, 43: 3175-3191. PMID: 38886581, PMCID: PMC11294477, DOI: 10.1038/s44318-024-00142-0.Peer-Reviewed Original ResearchLatrophilin-2Affinity purification methodCell-cell junctionsHuman genetic dataPECAM-1SiRNA screenGenetic dataEndothelial cell response to fluid shear stressGA proteinsDownstream eventsEndothelial-specific knockoutG-proteinActivity assayShear stress mechanotransductionPlexin-D1Endothelial signalingJunctional complexesPurification methodVE-cadherinResponse to fluid shear stressVascular developmentGA residuesEndothelial junctionsGPCRsVEGF receptors
2023
Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium
Ghersi J, Baldissera G, Hintzen J, Luff S, Cheng S, Xia I, Sturgeon C, Nicoli S. Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium. Nature Cell Biology 2023, 25: 1135-1145. PMID: 37460694, PMCID: PMC10415179, DOI: 10.1038/s41556-023-01187-9.Peer-Reviewed Original ResearchConceptsHaemogenic endothelial cellsHaematopoietic stemPost-transcriptional repressionHuman pluripotent stem cellsProgenitor cell heterogeneityCell cycle statePluripotent stem cellsG2/MZebrafish leadsAorta-gonadBlood lineagesEmbryonic endotheliumExpansion of HSPCsEndothelial cellsProliferative outputDifferent cell cycle statesLymphoid progenitorsCell heterogeneityLineagesMiR-128Jag1bHSPCsMyeloid lineageStem cellsCycle state3067 – HEMATOPOIETIC STEM AND PROGENITOR CELL HETEROGENEITY IS INHERITED FROM THE EMBRYONIC ENDOTHELIUM.
Ghersi J, Baldissera G, Hintzen J, Luff S, Cheng S, Xia I, Sturgeon C, Nicoli S. 3067 – HEMATOPOIETIC STEM AND PROGENITOR CELL HETEROGENEITY IS INHERITED FROM THE EMBRYONIC ENDOTHELIUM. Experimental Hematology 2023, 124: s83. DOI: 10.1016/j.exphem.2023.06.174.Peer-Reviewed Original ResearchHematopoietic stem/progenitor cellsMiR-128Hemogenic endothelial cellsMature blood cellsHuman pluripotent stem cellsCell cycle stateStem/progenitor cellsPluripotent stem cellsG2/MHematopoietic transitionEmbryonic endotheliumProliferative outputDifferent cell cycle statesAdult stageLymphoid progenitorsCell heterogeneityLineagesJag1bMyeloid lineageStem cellsProgenitor cellsCycle stateBlood progenitorsHemECsWnt
2021
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans
Barak T, Ristori E, Ercan-Sencicek AG, Miyagishima DF, Nelson-Williams C, Dong W, Jin SC, Prendergast A, Armero W, Henegariu O, Erson-Omay EZ, Harmancı AS, Guy M, Gültekin B, Kilic D, Rai DK, Goc N, Aguilera SM, Gülez B, Altinok S, Ozcan K, Yarman Y, Coskun S, Sempou E, Deniz E, Hintzen J, Cox A, Fomchenko E, Jung SW, Ozturk AK, Louvi A, Bilgüvar K, Connolly ES, Khokha MK, Kahle KT, Yasuno K, Lifton RP, Mishra-Gorur K, Nicoli S, Günel M. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans. Nature Medicine 2021, 27: 2165-2175. PMID: 34887573, PMCID: PMC8768030, DOI: 10.1038/s41591-021-01572-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPeptidyl-prolyl cis-transPathogenesis of IAContribution of variantsCommon genetic variantsVertebrate modelDeleterious mutationsWnt activatorAssociation studiesWhole-exome sequencingSignificant enrichmentGenetic variantsWntAngiogenesis regulatorsMutationsGene mutationsBrain angiogenesisIntracranial aneurysm ruptureJMJD6AngiogenesisCerebrovascular morphologyCerebrovascular integrityIntracerebral hemorrhageAneurysm ruptureVariants
2020
The N-glycome regulates the endothelial-to-hematopoietic transition
Kasper DM, Hintzen J, Wu Y, Ghersi JJ, Mandl HK, Salinas KE, Armero W, He Z, Sheng Y, Xie Y, Heindel DW, Park EJ, Sessa WC, Mahal LK, Lebrilla C, Hirschi KK, Nicoli S. The N-glycome regulates the endothelial-to-hematopoietic transition. Science 2020, 370: 1186-1191. PMID: 33273096, PMCID: PMC8312266, DOI: 10.1126/science.aaz2121.Peer-Reviewed Original ResearchMeSH KeywordsADAM10 ProteinAnimalsAnimals, Genetically ModifiedBeta-Galactoside alpha-2,3-SialyltransferaseCell LineageCell TransdifferentiationEndothelial CellsGenes, ReporterGlycomicsGlycoproteinsGlycosylationHematopoietic Stem CellsMannosyltransferasesMicroRNAsPolysaccharidesSialyltransferasesZebrafishConceptsHematopoietic transitionHemogenic endothelial cellsProtein N-glycosylationLymphoid-myeloid lineageN-glycomeDefinitive hematopoietic stemEndothelial cellsHematopoietic fateMiR-223Mutant defectsGlycan biosynthesisN-glycosylationMetalloprotease ADAM10Intrinsic regulatorN-glycoproteinsHematopoietic stemProgenitor cellsHigh mannoseMicroRNA-223CellsKey determinantMannosyltransferaseMutantsLineagesBiosynthesis