HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.08-112847v1 23/1/68    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gualandris, A. Articles by Bussolino, F. Search for Related Content PubMed PubMed Citation Articles by Gualandris, A. Articles by Bussolino, F.

Microenvironment drives the endothelial or neural fate of differentiating embryonic stem cells coexpressing neuropilin-1 and Flk-1

Anna Gualandris^*,,1,2, Alessio Noghero^*,,1, Massimo Geuna^,, Marco Arese^*,, Donatella Valdembri^*,, Guido Serini^*, and Federico Bussolino^*,

^* Division of Molecular Angiogenesis,

Division of Clinical and Experimental Cytometry, and

Department of Oncological Sciences, Institute for Cancer Research and Treatment (IRCC), University of Turin School of Medicine, Candiolo, Torino, Italy

² Correspondence: Department of Oncological Sciences, Institute for Cancer Research and Treatment (IRCC), Strada Provinciale 142, km 3,95, 10060, Candiolo (TO), Italy. E-mail: anna.gualandris{at}ircc.it

The observation that the architecture of the cardiovascular and nervous systems is drawn by common guidance cues and the closeness between neural progenitors and endothelial cells in the vascular niche strongly suggests the existence of links between endothelial and neural cell fates. We identified an embryonic stem cell-derived discrete, nonclonal cell population expressing the two vascular endothelial growth factor receptors neuropilin-1 (Nrp1) and Flk1 that differentiates in vitro toward endothelial or neural phenotypes depending on microenvironmental cues. When microinjected in the chick embryo, Nrp1⁺ cells integrate within the host, developing vessels and brain, and acquire endothelial and neural markers, respectively. These results show that precursors of endothelial cells and precursors of neural cells arise from the same pool of differentiating embryonic stem cells and share the expression of Nrp1 and Flk1. These data reinforce the parallelism between vascular and nervous system at the level of cell fate and commitment and open new perspective in regenerative medicine of neurovascular diseases.—Gualandris, A., Noghero, A., Geuna, M., Arese, M., Valdembri, D., Serini, G., Bussolino, F. Microenvironment drives the endothelial or neural fate of differentiating embryonic stem cells coexpressing neuropilin-1 and Flk-1.

Key Words: cell commitment • endothelial differentiation • embryoid bodies