TRANSHESC

Generation of stable transgenic embryonic stem cell lines

Coordinatore	THE UNIVERSITY OF SHEFFIELD    more  Organization address address: FIRTH COURT WESTERN BANK city: SHEFFIELD postcode: S10 2TN contact info Titolo: Ms. Nome: Deborah Cognome: Mcclean Email: send email Telefono: 441142000000 Fax: 441142000000
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	243˙268 €
EC contributo	243˙268 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2007-2-1-IEF
Funding Scheme	MC-IEF
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-09-01   -   2010-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE UNIVERSITY OF SHEFFIELD  Organization address address: FIRTH COURT WESTERN BANK city: SHEFFIELD postcode: S10 2TN contact info Titolo: Ms. Nome: Deborah Cognome: Mcclean Email: send email Telefono: 441142000000 Fax: 441142000000	UK (SHEFFIELD)	coordinator	0.00

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 Obiettivo del progetto (Objective)

'Human embryonic stem cells (hESC) are pluripotent cells derived from blastocyst stage early embryos. Since the original publication a vast number of studies have described the differentiation of hESC and their potential in regenerative medicine. It is now well known that hESC might be used in cell replacement therapies in a number of severe degenrative diseases like Type I diabetes or Parkinson’s disease. In addition, hESCs and their derivatives could be used as tools in discovering new drugs and in understanding mechanisms of genetic diseases. HESC applications could also be used in toxicological studies reducing the need of animal experiments. Genetic manipulation of hESC will be a crucial issue in a variety of future studies. To elucidate the role of any given gene for example in directed differentiation or pathogenesis the loss- and gain-of gene function approaches are of major importance. Also, considering the potential therapeutic applications of the hESC their genetic modifications may be necessary. The first part of this proposal is designed to improve and test novel efficient and safe transposon-based gene transfer method in generating conditional transgenic hESC lines. Of special interest is the use of insulator elements around transgene to assure nonbiased expression of the integrated sequences. Several reports have indicated that in long term hESC cultures the cells aquire chromosomal aberrations. The observed karyotypic changes probably reflect the progressive adaptation of self-renewing cells to their culture conditions. This process has parallels with malignant transformation. Changes observed in hESC in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors (TGCT). A recent report indicated the formation of a chromosomal homogeneous staining region (HSR) in some hESC lines, a feature almost a hallmark of cancer cells. The HSR represents an amplified small chromosomal region most likely containing gene'