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LYMPHORG SIGNED

Organ-specific mechanisms of lymphatic vascular development and specialisation

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EC-Contrib. €

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Project "LYMPHORG" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Project website http://www.makinenlab.com
 Total cost 2˙368˙439 €
 EC max contribution 2˙368˙439 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 2˙368˙439.00

Map

 Project objective

Lymphatic vasculature maintains tissue fluid homeostasis and has important emerging roles in inflammation, immunity, lipid metabolism, blood pressure regulation and cancer metastasis. Lymphatic vessels are specialised to fulfil the functional needs of different organs while diseases associated with lymphatic dysfunction frequently affect vessels of specific tissues. How functional specialisation of vessels is achieved and what underlies tissue-specific vessel failure is not understood. I hypothesise that organ-specific manifestation of lymphatic dysfunction in disease is due to vascular bed-specific differences in vessel formation. In this project my aim is to identify genes and mechanisms required for organ-specific lymphatic development. Building on our recent discovery of a previously unknown progenitor cell type that is required for lymphatic development in an organ-specific manner I set out to identify the origin and function of lymphatic endothelial progenitor cells (LEPC) during development and assess their potential for therapeutic lymphatic regeneration. Towards this aim, we will identify organ-specific origins of lymphatic vasculature using lineage tracing and determine genetic signatures of lymphatic endothelial progenitors by mRNA sequencing. Cells and tissues from normal and mutant mice that show organ-specific lymphatic defects will be analysed. To identify molecular and cellular mechanisms of LEPC derived vessel formation, we will functionally characterise LEPC signature genes using mouse models and visualise vessel development by in vivo two-photon microscopy. The function and therapeutic potential of LEPCs and LEPC derived vessels will be assessed using mouse models of tolerance, inflammation, obesity and lymphoedema. This work will provide novel insights into organ-specific mechanisms of vascular morphogenesis and identify a progenitor cell that may be expoited to restore lymphatic function in disorders associated with lymphatic vessel failure.

 Publications

year authors and title journal last update
List of publications.
2019 A. Álvarez-Aznar, I. Martínez-Corral, N. Daubel, C. Betsholtz, T. Mäkinen, K. Gaengel
Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreERT2 lines
published pages: , ISSN: 0962-8819, DOI: 10.1007/s11248-019-00177-8
Transgenic Research 2019-12-16
2018 Maike Frye, Andrea Taddei, Cathrin Dierkes, Ines Martinez-Corral, Matthew Fielden, Henrik Ortsäter, Jan Kazenwadel, Dinis P. Calado, Pia Ostergaard, Marjo Salminen, Liqun He, Natasha L. Harvey, Friedemann Kiefer, Taija Mäkinen
Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03959-6
Nature Communications 9/1 2019-05-30
2018 Yang Zhang, Nina Daubel, Simon Stritt, Taija Mäkinen
Transient loss of venous integrity during developmental vascular remodeling leads to red blood cell extravasation and clearance by lymphatic vessels
published pages: dev156745, ISSN: 0950-1991, DOI: 10.1242/dev.156745
Development 145/3 2019-05-31
2018 Yan Zhang, Maria H. Ulvmar, Lukas Stanczuk, Ines Martinez-Corral, Maike Frye, Kari Alitalo, Taija Mäkinen
Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03692-0
Nature Communications 9/1 2019-05-30
2016 Ines Martinez-Corral, Lukas Stanczuk, Maike Frye, Maria Helena Ulvmar, Rodrigo Diéguez-Hurtado, David Olmeda, Taija Makinen, Sagrario Ortega
Vegfr3-CreER T2 mouse, a new genetic tool for targeting the lymphatic system
published pages: 433-445, ISSN: 0969-6970, DOI: 10.1007/s10456-016-9505-x
Angiogenesis 19/3 2019-05-30
2017 Michael Potente, Taija Mäkinen
Vascular heterogeneity and specialization in development and disease
published pages: 477-494, ISSN: 1471-0072, DOI: 10.1038/nrm.2017.36
Nature Reviews Molecular Cell Biology 18/8 2019-05-30
2017 Yixin Wang, Yi Jin, Maarja Andaloussi Mäe, Yang Zhang, Henrik Ortsäter, Christer Betsholtz, Taija Mäkinen, Lars Jakobsson
Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity
published pages: 3590-3601, ISSN: 0950-1991, DOI: 10.1242/dev.147967
Development 144/19 2019-05-30
2016 Maria H. Ulvmar, Ines Martinez-Corral, Lukas Stanczuk, Taija Mäkinen
Pdgfrb-Cre targets lymphatic endothelial cells of both venous and non-venous origins
published pages: 350-358, ISSN: 1526-954X, DOI: 10.1002/dvg.22939
genesis 54/6 2019-05-30
2016 Maria H. Ulvmar, Taija Mäkinen
Heterogeneity in the lymphatic vascular system and its origin
published pages: 310-321, ISSN: 0008-6363, DOI: 10.1093/cvr/cvw175
Cardiovascular Research 111/4 2019-05-30

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