Induction of pancreatic phenotypes in central nervous system derived pluripotential progenitor cells.
Fetal rat brain stem cells (RSCs) have been induced to express pituitary properties when exposed to pituitary cells (U et al., 2002). In this study, we explored whether these RSCs could also be influenced to acquire properties characteristic of the pancreas. To this end, RSCs in culture were exposed to media conditioned by rat islet tumor cells and media containing Exendin-4 and nicotinamide since both have been shown to induce pancreatic phenotypes in embryonic stem cells. Lastly, an expression construct for pdx-1 was introduced into RSCs. The expression of pancreatic markers was analyzed using RT-PRC and immunocytochemistry. When RSCs were exposed to rat islet tumor cell conditioned media and media containing Exendin-4 and nicotinamide, the expression of pdx-1, insulin and somatostatin were observed. They also acquired a spherical shape typical of pancreatic cells in culture. Under these varied conditions, transcriptional factors essential to pancreatic development such as pdx-1 and Isl-1 were induced. The critical role of pdx-1 in stimulating certain endocrine pancreatic properties in RSCs was further confirmed upon the introduction of an expression construct for pdx-1 which markedly induced insulin and somatostatin. Taken together, these findings suggests that fetal brain stem cells are pluripotent and can be reprogrammed to acquire pancreatic properties through pathways which involved the transcription factor Pdx1.
Saljooque
F
F
Division of Neurological Surgery, Veterans Administration San Diego Health Care System and The University of California - San Diego, San Diego, California, USA.
Ho
A
A
Wu
B
B
Zahra
A
A
U
H S
HS
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D004622:Embryo, Mammalian; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
D015415:Biomarkers; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; D013004:Somatostatin