. . "1"^^ . . "1"^^ . "2010-01-01+01:00"^^ . . "0"^^ . . . . . "2014-09-08+02:00"^^ . . . "apoptosis TRAIL Fas signaling differentiation stress oncogenes"@en . "Human embryonic stem cells (hESCs) and recently also the human induced pluripotent stem cells (iPSCs) brought significant attention and raised hopes for the replacement therapy of serious human disease as well as for the potential in vitro histo\u2013 and organo-neogenesis. Though our knowledge of signaling pathways underlying the self-renewal, immortality and directed differentiation of the stem cells vastly increased during the past 10 years, the activation and regulation of another ultimate process \u2013 apoptosis of hESCs, is far from being fully comprehended. Death receptors (DRs) of the TNFR family represent the most important and efficient extrinsic apoptosis machinery and play an important role in the immune, stress and anti-tumour responses. Virtually nothing is known about the function and regulation of DRs in hESCs. In the proposed project we shall undertake complex analysis of main DRs (Fas/CD95, TNFR1 and TRAIL receptors) expression, signaling and regulation in hES cell lines under normal and stressed conditions (e.g. DNA damage, activation of oncogenes or oxidative stress) and in cells differentiating to defined lineages. The results of our study will not only widen our DRs-related knowledge but could be also used for targeted elimination of hESC in risk."@en . "Exprese, signalizace a funkce receptor\u016F smrti v lidsk\u00FDch embryon\u00E1ln\u00EDch kmenov\u00FDch bu\u0148k\u00E1ch." . . . . . "GAP301/10/1971" . . . . "5"^^ . "Expression, signaling and function of Death Receptors in human embryonic stem cells."@en . . "5"^^ . . "http://www.isvav.cz/projectDetail.do?rowId=GAP301/10/1971"^^ . "Lidsk\u00E9 embryon\u00E1ln\u00ED kmenov\u00E9 bu\u0148ky (hESC) a nov\u011B tak\u00E9 lidsk\u00E9 indukovan\u00E9 pluripotentn\u00ED kmenov\u00E9 bu\u0148ky (iPSC) vzbudily v\u00FDrazn\u00FD v\u011Bdeck\u00FD z\u00E1jem a vyvolaly nad\u011Bje z pohledu jejich mo\u017En\u00E9ho pou\u017Eit\u00ED pro terapii z\u00E1va\u017En\u00FDch lidsk\u00FDch onemocn\u011Bn\u00ED, p\u0159\u00EDpadn\u011B tvorbu tk\u00E1n\u00ED a org\u00E1n\u016F ex vivo. A\u010Dkoli na\u0161e pochopen\u00ED sign\u00E1ln\u00EDch drah zodpov\u011Bdn\u00FDch za schopnost sebeobnovy a diferencia\u010Dn\u00ED potenci\u00E1l hESC v posledn\u00ED dek\u00E1d\u011B v\u00FDrazn\u011B vzrostlo, mechanismy aktivace a regulace dal\u0161\u00EDho v\u00FDznamn\u00E9ho procesu - bun\u011B\u010Dn\u00E9 smrti hESC, z\u016Fst\u00E1vaj\u00ED experiment\u00E1ln\u011B t\u00E9m\u011B\u0159 netknuty. Receptory smrti (DR) z rodiny TNFR jsou nejv\u00FDznamn\u011Bj\u0161\u00EDmi hr\u00E1\u010Di v tomto procesu a uplat\u0148uj\u00ED se v imunitn\u00ED, protistresov\u00E9 a protin\u00E1dorov\u00E9 odpov\u011Bdi. O funkci t\u011Bchto molekul u hESC nen\u00ED dosud nic zn\u00E1mo. Obsahem navrhovan\u00E9ho projektu je proto komplexn\u00ED anal\u00FDza exprese, signalizace a funkce hlavn\u00EDch DR (Fas/CD95, TNFR1 a TRAIL receptor\u016F) v hESC a z nich diferencovan\u00FDch deriv\u00E1t\u016F za norm\u00E1ln\u00EDch i stresov\u00FDch podm\u00EDnek (nap\u0159. po\u0161kozen\u00ED DNA, aktivace onkogen\u016F, oxida\u010Dn\u00ED stres). V\u00FDsledky studie p\u0159inesou nejen z\u00E1kladn\u00ED poznatky o funkc\u00EDch DR v tomto unik\u00E1tn\u00EDm bun\u011B\u010Dn\u00E9m typu, ale mohou tak\u00E9 p\u0159isp\u011Bt k n\u00E1vrhu c\u00EDlen\u00E9 eliminace rizik spojen\u00FDch s abnorm\u00E1ln\u00EDm chov\u00E1n\u00EDm hESC bun\u011Bk p\u0159i jejich pou\u017Eit\u00ED v terapii." .