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TGFβ1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells
Author(s) -
Vittet Daniel,
Merdzhanova Galina,
Prandini MarieHélène,
Feige JeanJacques,
Bailly Sabine
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24063
Subject(s) - lymphatic system , lymphatic endothelium , embryonic stem cell , stromal cell , biology , vascular endothelial growth factor c , microbiology and biotechnology , endothelial stem cell , stem cell , transforming growth factor , immunology , cancer research , vascular endothelial growth factor a , vascular endothelial growth factor , genetics , vegf receptors , in vitro , gene
The lymphatic vasculature is essential for the maintenance of tissue fluid, immune surveillance, and dissemination of metastasis. Recently, several models for lymphatic vascular research and markers specific for lymphatic endothelium have been characterized. Despite these significant achievements, our understanding of the early lymphatic development is still rather limited. The purpose of the study was to further define early lymphatic differentiation regulatory pathways. In the present study, we have developed conditions leading to lymphatic endothelial cell differentiation under both serum‐rich and serum‐free conditions, using the coculture system of Flk‐1‐positive vascular precursors derived from murine embryonic stem (ES) cells grown on an OP9 stromal cell layer. In this work, we also identified Transforming Growth Factor‐β1 (TGFβ1) as a negative regulator of lymphvasculogenesis from ES‐derived vascular progenitors. Finally, we could show that TGFβ1 addition decreases COUP‐TFII and Sox18 mRNA levels, which are two transcription factors known to be involved in early lymphatic endothelial differentiation. Taken together these findings support the concept that manipulating the TGFβ signaling pathway may represent an interesting target to favor lymphatic endothelial cell expansion for cell replacement strategies. J. Cell. Physiol. 227: 3593–3602, 2012. © 2012 Wiley Periodicals, Inc.