"HMGB proteins: involvement in biology of telomeres and human embryonic stem cells"@en . . "1"^^ . "Recently we have observed that deficiency of chromosomal HMGB1 protein (involved in transcription, DNA repair, genomic stability and cellular signaling) in mouse fibroblasts resulted in significant decrease in telomerase activity, shortening of telomere length and chromosome aberrations. Here we propose to study the impact of deregulated expression of HMGB1 or other HMGBs (silencing by shRNA or plasmid-directed over-expression) in stably transfected human embryonic stem cells (hESCs). As HMGB1 expression becomes down-regulated upon entry of hESCs into differentiation pathway, we will address the possible involvement of HMGBs in maintenance of the key property of stem cells - pluripotency. We also intend to study the involvement of HMGBs in modulation of telomerase activity, telomere functioning and genomic stability. This project is based on rather distant fields of molecular and biomedical sciences, and it is expected to produce results of basic research which may also be relevant to biomedical application of hESCs which is often limited by genetic instability of the stem cells."@en . "GAP305/12/2475" . . . "2015-12-31+01:00"^^ . . . . . . . "http://www.isvav.cz/projectDetail.do?rowId=GAP305/12/2475"^^ . . . "2014-04-28+02:00"^^ . "Proteiny HMGB: funkce v biologii telomer a lidsk\u00FDch embryon\u00E1ln\u00EDch kmenov\u00FDch bun\u011Bk" . "2012-01-01+01:00"^^ . "HMGB proteins chromatin telomeres genomic stability pluripotency differentiation human embryonic stem cells"@en . . . . "0"^^ . . "2015-04-23+02:00"^^ . "2"^^ . . . "2"^^ . "Ned\u00E1vno jsme prok\u00E1zali, \u017Ee inhibice exprese chromozom\u00E1ln\u00EDho proteinu HMGB1 (v\u00FDznamn\u00FD pro transkripci, reparaci DNA, genomovou stabilitu a bun\u011B\u010Dnou signalizaci) vede u my\u0161\u00EDch fibroblast\u016F k v\u00FDznamn\u00E9mu poklesu aktivity telomer\u00E1zy, zkr\u00E1cen\u00ED telomer a chromozomov\u00FDm aberac\u00EDm. V tomto projektu navrhujeme studovat c\u00EDlenou deregulaci exprese protein\u016F HMGB (\u00FAtlum vlivem shRNA nebo zv\u00FD\u0161en\u00ED exprese vlivem plazmidu) v stabiln\u011B transfekovan\u00FDch lidsk\u00FDch embryon\u00E1ln\u00EDch kmenov\u00FDch bu\u0148k\u00E1ch (hESCs). Vzhledem k tomu, \u017Ee v pr\u016Fb\u011Bhu diferenciace hESCs doch\u00E1z\u00ED k \u00FAtlumu exprese HMGB1, budeme sledovat vliv deregulace exprese HMGB1 (pop\u0159. jin\u00FDch protein\u016F rodiny HMGB) na zachov\u00E1n\u00ED kl\u00ED\u010Dov\u00E9 vlastnosti kmenov\u00FDch bun\u011Bk - pluripotence. D\u00E1le budeme studovat vliv protein\u016F HMGB na aktivitu telomer\u00E1zy, strukturu/funkci telomer a genomovou stabilitu. Navrhovan\u00FD projekt je zalo\u017Een na spojen\u00ED relativn\u011B odli\u0161n\u00FDch oblast\u00ED z\u00E1kladn\u00EDho v\u00FDzkumu v oblasti molekul\u00E1rn\u00ED a l\u00E9ka\u0159sk\u00E9 biologie s c\u00EDlem z\u00EDskat v\u00FDsledky nejen z\u00E1kladn\u00EDho v\u00FDzkumu, ale i pro mo\u017En\u00E9 vyu\u017Eit\u00ED v medic\u00EDn\u011B, kter\u00E9 je \u010Dasto limitov\u00E1no genetickou nestabilitou hESCs." . . "1"^^ .