Guided differentiation of embryonic stem cells into Pdx1-expressing regional-specific definitive endoderm.
The generation of specific lineages of the definitive endoderm from embryonic stem (ES) cells is an important issue in developmental biology, as well as in regenerative medicine. This study demonstrates that ES cells are induced sequentially into regional-specific gut endoderm lineages, such as pancreatic, hepatic, and other cell lineages, when they are cultured directly on a monolayer of mesoderm-derived supporting cells. A detailed chronological analysis revealed that Activin, fibroblast growth factor, or bone morphogenetic protein signals are critical at various steps and that additional short-range signals are required for differentiation into Pdx1-expressing cells. Under selective culture conditions, definitive endoderm (47%) or Pdx1-positive pancreatic progenitors (30%) are yielded at a high efficiency. When transplanted under the kidney capsule, the Pdx1-positive cells further differentiated into all three pancreatic lineages, namely endocrine, exocrine, and duct cells.
Shiraki
Nobuaki
N
Division of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
Yoshida
Tetsu
T
Araki
Kimi
K
Umezawa
Akihiro
A
Higuchi
Yuichiro
Y
Goto
Hideo
H
Kume
Kazuhiko
K
Kume
Shoen
S
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D004707:Endoderm / Q000166:cytology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D033581:Stem Cell Transplantation / Q000379:methods; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein