Programming embryonic stem cell derived endodermal cells towards a Beta cell phenotype. (360G-Wellcome-080241_Z_06_Z)

£251,649

The aim of this project is to develop a protocol whereby human embryonic stem cells (hESCs) can be induced to differentiate into insulin secreting Beta cells. The hESCs will be cultured in chemically defined media in the presence of growth factors that promote differentiation of endoderm. We will also generate hESC lines that have been stably transfected with DNA constructs in which fluorescent reporter proteins are expressed under the control of regulatory sequences of genes encoding transcrip tion factors that control beta cell differentiation. These lines will be used to optimise culture conditions for the differentiation of endoderm-enriched hESCs towards Beta cells. To assure differentiation towards a Beta cell like phenotype we propose to induce expression of transcription factors that are known to control islet development. We have constructed a novel plasmid in which a superactive form of the transcription factor PDX1, i.e. PDX1VP16 is fused to a 4 OH-tamoxifen responsive seq uence, ERT2. The plasmid is configured such a way that it should be possible to replace the PDX1 coding sequences with sequences for PAX4, BETA2, ngn3 or other factors that are known to control islet cell differentiation. The hESC-derived Beta cells will be characterised in vitro and in mouse diabetic models.

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Grant Details

Amount Awarded 251649
Applicant Surname Docherty
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2006-06-27T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 080241/Z/06/Z
Lead Applicant Prof Kevin Docherty
Other Applicant(s) Prof Ludovic Vallier, Prof Roger Pedersen
Partnership Value 251649
Planned Dates: End Date 2009-01-31T00:00:00+00:00
Planned Dates: Start Date 2006-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland