From: Subject: Bio.com -- Biotech, Biotechnology and Pharmaceutical News and Featured Articles Date: Wed, 5 Feb 2003 09:53:44 -0000 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_0000_01C2CCFC.78C0EE90"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V5.50.4522.1200 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C2CCFC.78C0EE90 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?action=view&contentItem=100007258&Page=1 Bio.com -- Biotech, Biotechnology and Pharmaceutical = News and Featured Articles
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 =20
Sealing a Cell's Fate =

2/4/2003 -- A collaboration of = scientists,=20 led by Dr. Janet Rossant at the University of Toronto = and The=20 Samuel Lunenfeld Research Institute at Mount Sinai = Hospital,=20 has identified two genes whose combined expression = drives the=20 development of the blood and blood vessels in early=20 embryogenesis. This discovery lends new insight into = the=20 molecular cues that direct blood and vascular = development -- a=20 crucial event in both normal and pathological = processes, like=20 tumor angiogenesis. Their results were published in Genes &=20 Development.

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Dr. Rossant and colleagues have = discovered that=20 the proteins encoded by two genes, called Flk1 and = Tal1, coax=20 embryonic progenitor cells to become either cells that = compose=20 the blood (hematopoietic cells), line the blood = vessels=20 (endothelial cells), or help support the blood vessel = walls=20 (smooth muscle cells). While it has been hypothesized = that=20 endothelial and hematopoietic cells are derived from a = common=20 progenitor cell, called the hemangioblast, Dr. Rossant = and=20 colleagues now show that the co-expression of Flk1 and = Tal1 in=20 the hemangioblast is necessary for normal endothelial, = hematopoietic, and smooth muscle cell specification. =

"We are interested in trying to = understand the=20 relationships between cells of the blood, and the = cells lining=20 the blood vessels in which they are transported. = Surprisingly,=20 our studies and those of others suggest that, at least = in the=20 early embryo, these two cells come from a common = progenitor,=20 the hemangioblast. What is more, the same progenitor = can give=20 rise to the smooth muscle cells of the vessel walls," = explains=20 Dr. Rossant

Flk1 encodes a cell surface receptor = for the=20 vascular endothelial growth factor (VEGF), a crucial = factor in=20 angiogenesis. Transgenic mice lacking Flk1 fail to = form=20 endothelial and hematopoietic cells, and also fail to = express=20 the transcription factor Tal1. To test the effect of = Tal1 on=20 hemangioblast development, Dr. Rossant and colleagues=20 reintroduced Tal1 into Flk1-deficient mouse embryos = and=20 embryonic stem (ES) cells.

These Tal1-expressing, Flk1-deficient = mouse=20 embryos still died in utero, but the development of=20 endothelial and hematopoietic cells was improved. More = marked,=20 though, was the ability of Tal1-expressing, = Flk1-deficient ES=20 cells to differentiate into hematopoietic cells at = levels=20 comparable to that of ES cells missing only one copy = of Flk1=20 (Flk1-heterozygous ES cells). The researchers also = expressed=20 additional Tal1 in Flk1-heterozygous ES cells, and = found that=20 this enhanced expression of Tal1 both augmented the = cells'=20 hematopoietic potential and enabled the cells to = differentiate=20 into smooth muscle cells.

Taken together, these findings provide = further=20 support for the existence of a common hemangioblast = progenitor=20 cell, in which the dual expression of Flk1 and Tal1 = steer=20 cells into a path of either endothelial, = hematopoietic, or=20 smooth muscle cell fate.

"Using mouse embryonic stem cells we = have been=20 able to manipulate the proportions of the three = different cell=20 types arising from the hemangioblast by altering = expression of=20 a signaling pathway and one of its downstream effector = molecules. These kinds of studies will help us = understand how=20 to manipulate human stem cells for therapeutic uses in = vascular damage and disease," states Dr. Rossant.

Source: Cold Spring Harbor = Laboratory


   
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1px solid; COLOR: #ffffff; FONT-FAMILY: Arial, = Helvetica; FONT-SIZE: 12px; PADDING-BOTTOM: 3px; PADDING-LEFT: 3px; = PADDING-RIGHT: 3px; PADDING-TOP: 3px; POSITION: absolute; VISIBILITY: = hidden; WIDTH: 200px } DIV.joinforfree { BACKGROUND-COLOR: #ffffcc; BORDER-BOTTOM: #999999 1px solid; = BORDER-LEFT: #999999 1px solid; BORDER-RIGHT: #999999 1px solid; = BORDER-TOP: #999999 1px solid; COLOR: #000000; FONT-FAMILY: Arial, = Helvetica; FONT-SIZE: 12px; PADDING-BOTTOM: 3px; PADDING-LEFT: 3px; = PADDING-RIGHT: 3px; PADDING-TOP: 3px; POSITION: absolute; VISIBILITY: = hidden; WIDTH: 175px } INPUT.small { COLOR: #000000; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 10px } SELECT.small { COLOR: #000000; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 10px } .storeLeftHandNav { BACKGROUND-COLOR: #faf3d5 } .storeBreadcrumb { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; FONT-WEIGHT: normal; = TEXT-DECORATION: none } .storeBreadcrumbSelected { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; FONT-WEIGHT: bold; = TEXT-DECORATION: none } .storeInternalHeader { BACKGROUND-COLOR: #faf3d5; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: = 12px; TEXT-DECORATION: none } .storeInternalWhiteHeader { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; TEXT-DECORATION: none } .storeSearch { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 10px } .storeSearchElementHeader { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 10px } .storeShadedHeader { BACKGROUND-COLOR: #ece2cd; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: = 12px; FONT-WEIGHT: bold } .storeShadedRow { BACKGROUND-COLOR: #faf3d5; FONT-FAMILY: Arial, Helvetica } .storeUnshadedRow { BACKGROUND-COLOR: #ffffff; FONT-FAMILY: Arial, Helvetica } .storeDarkBackground { BACKGROUND-COLOR: #644347 } .storePagingBackground { BACKGROUND-COLOR: #faf3d5 } .storeColumnCart { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 11px } .storeSmall { FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 11px } .storeSmallGrey { COLOR: #666666; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 11px } .storeHeader { COLOR: #644347; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 16px; = FONT-WEIGHT: bold; TEXT-DECORATION: none } .storeHeaderSmall { COLOR: #644347; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; = FONT-WEIGHT: bold; TEXT-DECORATION: none } .storeOrange { COLOR: #df941f } .checkoutheaders { COLOR: #765559; FONT-SIZE: 11px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } .storeSmallLink { FONT-SIZE: 10px } A.smallstore { COLOR: #644347; FONT-SIZE: 10px } A.contentheaderstore { COLOR: #644347; FONT-WEIGHT: bold; TEXT-DECORATION: none } A.storefeaturelink { COLOR: #644347; FONT-SIZE: 12px; TEXT-DECORATION: none } A.contentheaderstoresmall { COLOR: #644347; FONT-SIZE: 12px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } .contentheaderaboutbio { COLOR: #7e643a; FONT-SIZE: 14px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } .tao { COLOR: #7e643a } A.contentheaderaboutbio { COLOR: #7e643a; FONT-WEIGHT: bold; TEXT-DECORATION: none } A.smallaboutbio { COLOR: #706446; FONT-SIZE: 10px } A.centeraboutbio { COLOR: #7e643a; FONT-SIZE: 12px; TEXT-DECORATION: none } .contentheadercareercenter { COLOR: #978948; FONT-SIZE: 14px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } .contentheadersmall { COLOR: #978948; FONT-SIZE: 12px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } A.homeLinksCareerCenter { COLOR: #336699; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; = TEXT-DECORATION: none; outline: none } A.homeLinksCareerCenter:hover { COLOR: #336699; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: 12px; = TEXT-DECORATION: underline; outline: none } A.smallcareercenter { COLOR: #978948; FONT-SIZE: 10px } A.contentheadercareercenter { COLOR: #978948; FONT-WEIGHT: bold; TEXT-DECORATION: none } A.contentcareercenter { COLOR: #978948; FONT-SIZE: 12px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } A.contentselected { COLOR: #336699 } A.contentheadernewsfeatures { COLOR: #474157; FONT-WEIGHT: bold; TEXT-DECORATION: none } A.newsfeatures { COLOR: #474157 } .contentheadernewsfeatures { COLOR: #474157; FONT-WEIGHT: bold; TEXT-DECORATION: none } I.smallnewsfeatures { COLOR: #474157; FONT-SIZE: 10px } A.contentheaderindustry { COLOR: #5d7c4f; FONT-WEIGHT: bold; TEXT-DECORATION: none } .stockquotes { COLOR: #5d7c4f; FONT-WEIGHT: bold; TEXT-DECORATION: none; = TEXT-TRANSFORM: uppercase } .inverted { COLOR: #ffffff } .profiles { COLOR: #5d7c4f } I.smallindustry { COLOR: #5d7c4f; FONT-SIZE: 10px } I.tagline { COLOR: #5d7c4f; FONT-STYLE: italic } TD.contentheaderindustrynolink { COLOR: #5d7c4f; FONT-WEIGHT: bold; TEXT-DECORATION: none } TD.companyheader { COLOR: #000000; FONT-SIZE: 22px; FONT-WEIGHT: bold; TEXT-DECORATION: = none } .industryAnalysisShadedRow { BACKGROUND-COLOR: #e1edd7; FONT-FAMILY: Arial, Helvetica } .industryAnalysisInternalHeader { BACKGROUND-COLOR: #e1edd7; FONT-FAMILY: Arial, Helvetica; FONT-SIZE: = 12px; TEXT-DECORATION: none } .industryAnalysisLeftHandNav { BACKGROUND-COLOR: #e1edd7 } A.resourcelinks { COLOR: #557672 } .highlight { COLOR: #2f4946; 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------=_NextPart_000_0000_01C2CCFC.78C0EE90 Content-Type: application/x-javascript Content-Transfer-Encoding: 7bit Content-Location: http://www.bio.com/js/menu_rollovers.js // layer functoins and initialization of top nav layers function getObjectForEvents (obj) { var theObj; if (typeof obj == "string") { if (isNav6) { theObj = document.getElementById(obj); } else { theObj = eval("document." + range + obj); } } else { theObj = obj; } return theObj; } for (var i = 0; i < navComponents.length; i++) { eval("initObj = getObjectForEvents('" + navComponents[i] + "div')"); initObj.rollname = navComponents[i]; initObj.mousedover = false; initObj.onmouseover = onDiv; initObj.onmouseout = offDiv; } function getObject (obj) { var theObj; if (typeof obj == "string") { if (isNav6) { theObj = document.getElementById(obj).style; } else { theObj = eval("document." + range + obj + styleObj); } } else { theObj = obj; } return theObj; } function shiftTo(obj, x, y) { var theObj = getObject(obj); if 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"div').mousedover = false"); eval("document.images." + which + ".src = " + which + "on.src"); setTimeout("navFinishUnRoll('"+ which +"')", 500); } function navFinishUnRoll (which) { if (!eval("getObjectForEvents('" + which + "div').mousedover")) { eval("document.images." + which + ".src = " + which + "off.src"); eval("hide('" + which + "div')"); } } // functoins for right side naviagtion function rightNavRoll (which) { if (which != "joinforfree") { eval("document.images." + which + ".src = " + which + "on.src"); eval("getObject('" + which + "div').bgColor = '#4E5B6D'"); } else { eval("getObject('" + which + "div').bgColor = '#FFFFCC'"); } eval("show('" + which + "div')"); } function rightNavUnRoll (which) { if (which != "joinforfree") { eval("document.images." + which + ".src = " + which + "off.src"); } eval("hide('" + which + "div')"); } ------=_NextPart_000_0000_01C2CCFC.78C0EE90--