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

Standard

Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. / Frye, Maike; Taddei, Andrea; Dierkes, Cathrin; Martinez-Corral, Ines; Fielden, Matthew; Ortsäter, Henrik; Kazenwadel, Jan; Calado, Dinis P; Ostergaard, Pia; Salminen, Marjo; He, Liqun; Harvey, Natasha L; Kiefer, Friedemann; Mäkinen, Taija.

in: NAT COMMUN, Jahrgang 9, Nr. 1, 17.04.2018, S. 1511.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Frye, M, Taddei, A, Dierkes, C, Martinez-Corral, I, Fielden, M, Ortsäter, H, Kazenwadel, J, Calado, DP, Ostergaard, P, Salminen, M, He, L, Harvey, NL, Kiefer, F & Mäkinen, T 2018, 'Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program', NAT COMMUN, Jg. 9, Nr. 1, S. 1511. https://doi.org/10.1038/s41467-018-03959-6

APA

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. NAT COMMUN, 9(1), 1511. https://doi.org/10.1038/s41467-018-03959-6

Vancouver

Bibtex

@article{6363702e4db1479880cbc99f9ed64175,
title = "Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program",
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.",
keywords = "Journal Article",
author = "Maike Frye and Andrea Taddei and Cathrin Dierkes and Ines Martinez-Corral and Matthew Fielden and Henrik Orts{\"a}ter and Jan Kazenwadel and Calado, {Dinis P} and Pia Ostergaard and Marjo Salminen and Liqun He and Harvey, {Natasha L} and Friedemann Kiefer and Taija M{\"a}kinen",
year = "2018",
month = apr,
day = "17",
doi = "10.1038/s41467-018-03959-6",
language = "English",
volume = "9",
pages = "1511",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program

AU - Frye, Maike

AU - Taddei, Andrea

AU - Dierkes, Cathrin

AU - Martinez-Corral, Ines

AU - Fielden, Matthew

AU - Ortsäter, Henrik

AU - Kazenwadel, Jan

AU - Calado, Dinis P

AU - Ostergaard, Pia

AU - Salminen, Marjo

AU - He, Liqun

AU - Harvey, Natasha L

AU - Kiefer, Friedemann

AU - Mäkinen, Taija

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41467-018-03959-6

DO - 10.1038/s41467-018-03959-6

M3 - SCORING: Journal article

C2 - 29666442

VL - 9

SP - 1511

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -