Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program

Show simple item record

dc.contributor.author Frye, Maike
dc.contributor.author Taddei, Andrea
dc.contributor.author Dierkes, Cathrin
dc.contributor.author Martinez-Corral, Ines
dc.contributor.author Fielden, Matthew
dc.contributor.author Ortsäter, Henrik
dc.contributor.author Kazenwadel, Jan
dc.contributor.author Calado, Dinis P.
dc.contributor.author Ostergaard, Pia
dc.contributor.author Salminen, Marjo
dc.contributor.author He, Liqun
dc.contributor.author Harvey, Natasha L.
dc.contributor.author Kiefer, Friedemann
dc.contributor.author Mäkinen, Taija
dc.date.accessioned 2018-05-09T09:27:02Z
dc.date.available 2018-05-09T09:27:02Z
dc.date.issued 2018-04-17
dc.identifier.citation Frye , M , Taddei , A , Dierkes , C , Martinez-Corral , I , Fielden , M , Ortsäter , H , Kazenwadel , J , Calado , D P , Ostergaard , P , Salminen , M , He , L , Harvey , N L , Kiefer , F & Mäkinen , T 2018 , ' Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program ' , Nature Communications , vol. 9 , 1511 . https://doi.org/10.1038/s41467-018-03959-6
dc.identifier.other PURE: 106399382
dc.identifier.other PURE UUID: dfb162ad-5bb2-40a0-9cfe-46007350d5d5
dc.identifier.other WOS: 000430196200006
dc.identifier.other Scopus: 85045756989
dc.identifier.other ORCID: /0000-0003-0696-6845/work/44717789
dc.identifier.uri http://hdl.handle.net/10138/234754
dc.description.abstract Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development. en
dc.format.extent 16
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ENDOTHELIAL-CELL PROGENITORS
dc.subject SIGNALING PATHWAY
dc.subject VALVE DEVELOPMENT
dc.subject LAMINAR-FLOW
dc.subject IN-VIVO
dc.subject LYMPHANGIOGENESIS
dc.subject GROWTH
dc.subject GATA2
dc.subject MOUSE
dc.subject VASCULATURE
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program en
dc.type Article
dc.contributor.organization Departments of Faculty of Veterinary Medicine
dc.contributor.organization Marjo Salminen / Principal Investigator
dc.contributor.organization Veterinary Biosciences
dc.contributor.organization Veterinary Biochemistry and Cell Biology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41467-018-03959-6
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
Frye_et_al_2018_Nature_Communications.pdf 7.510Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record