In vitro induction of adult hepatic progenitor cells into insulin-producing cells.
Organ-specific stem cells are the natural progenitors in tissue regeneration and possess plasticity to differentiate into specialized cells in adult tissues. Small hepatocytes (SHCs) identified in the adult liver are one such cell type. Here we show that SHCs, which are capable of self-renewal and differentiation into hepatocytes, can be induced to generate insulin-producing cells under appropriate culture conditions. These differentiated cells express pancreatic beta cell differentiation-related transcripts and hepatocyte differentiation-related transcripts, as shown by reverse-transcription PCR/nested PCR. In addition, enforced expression of the homeodomain transcription factor Pdx1 in these cells contributes to enhancement of insulin release in response to insulin secretagogues. These results indicate that the SHCs described here have the ability to differentiate into insulin-producing cells, and further support the idea that engineering to generate insulin-secreting cells could provide a useful resource for future therapies for diabetes mellitus.
Nakajima-Nagata
Natsuki
N
Center for Molecular Biology and Genetics, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Sakurai
Tomonori
T
Mitaka
Toshihiro
T
Katakai
Tomoya
T
Yamato
Eiji
E
Miyazaki
Jun-ichi
J
Tabata
Yasuhiko
Y
Sugai
Manabu
M
Shimizu
Akira
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D020869:Gene Expression Profiling; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000166:cytology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018398:Homeodomain Proteins; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D014044:Tolbutamide; D005947:Glucose; D011188:Potassium