Editorial |
From the Department of Pathology, University of Washington, Seattle, Wash.
Correspondence to Stephen M. Schwartz, MD, PhD, Vascular Biology, Box 357335, University of Washington, Seattle, WA 98195-7335. E-mail steves@u.washington.edu
Key Words: array display cell lineage differentiation cell type
What do we mean by "cell type?" Two articles in this issue of Circulation Research address this question in different ways. The first study, by Dube et al,1 uses very well-defined tools to define endothelial differentiation at the level of transcriptional control. The second study, by Kowal et al,2 looks for novel genes that distinguish two cell types. These studies, taken together, illustrate a major change in how we define cell type, a change that is about to be accelerated by the power of systematic genomics.
Dube et al1 use in vitro systems to explore the promoter structure for the endothelial cell-specific receptor tyrosine kinase Tie2. Tie2 is a receptor for both angiopoetin-1 and angiopoetin-2. Like vascular endothelial growth factor, angiopoetin-1 is essential for normal vascular development whereas angiopoetin-2 is a naturally occurring antagonist for angiotensin I and Tie2. Thus, regulation of expression of the Tie2 receptor is likely a key issue in the formation of blood vessels.3 4 Dube et al1 identify a putative Ets transcription site in the Tie2 promoter. One of the proteins binding to this site, NERF2, can be shown to promote transcription in endothelial cells but not in the other cells studied. Related NERFs and other Ets binding factors either did not have this activity or were not found in the cultured cells used by these authors.
Although mechanistically solid for transfected
endothelial cell lines in vitro, the studies
presented by Dube et al1 provide no
evidence that NERF2 is expressed in endothelial cells
in vivo,
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