Generation of insulin-expressing cells from mouse embryonic stem cells.
The therapeutic potential of transplantation of insulin-secreting pancreatic beta-cells has stimulated interest in using pluripotent embryonic stem (ES) cells as a starting material from which to generate insulin secreting cells in vitro. Mature beta-cells are endodermal in origin so most reported differentiation protocols rely on the identification of endoderm-specific markers. However, endoderm development is an early event in embryogenesis that produces cells destined for the gut and associated organs in the embryo, and for the development of extra-embryonic structures such as the yolk sac. We have demonstrated that mouse ES cells readily differentiate into extra-embryonic endoderm in vitro, and that these cell populations express the insulin gene and other functional elements associated with beta-cells. We suggest that the insulin-expressing cells generated in this and other studies are not authentic pancreatic beta-cells, but may be of extra-embryonic endodermal origin.
Milne
Helen M
HM
Beta Dell Development and Function Group, Division of Reproductive Health Endocrinology and Development, GKT School of Biomedical Sciences, King's College London, London SE1 1UL, UK.
Burns
Christopher J
CJ
Kitsou-Mylona
Isidora
I
Luther
Melanie J
MJ
Minger
Stephen L
SL
Persaud
Shanta J
SJ
Jones
Peter M
PM
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D050814:Octamer Transcription Factor-3; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D007328:Insulin; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors