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TGFβ1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells

Identifieur interne : 000239 ( France/Analysis ); précédent : 000238; suivant : 000240

TGFβ1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells

Auteurs : Daniel Vittet [France] ; Galina Merdzhanova [France] ; Marie-Hélène Prandini [France] ; Jean-Jacques Feige [France] ; Sabine Bailly [France]

Source :

RBID : ISTEX:C4D37925D3FCE9FD2D09E1DA3079E282CE0DFA00

Abstract

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.

Url:
DOI: 10.1002/jcp.24063


Affiliations:


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ISTEX:C4D37925D3FCE9FD2D09E1DA3079E282CE0DFA00

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