Pituitary transcription factor-1 induces transient differentiation of adult hepatic stem cells into prolactin-producing cells in vivo.
A subset of transcription factors function as pivotal regulators of cell differentiation pathways. Pituitary transcription factor-1 (Pit-1) is a tissue-specific homeodomain protein that specifies the development of pituitary somatotropes and lactotropes. In this study, adenovirus was used to deliver rat Pit-1 to mouse liver. Pit-1 expression was detected in the majority (50-80%) of hepatocyte nuclei after tail vein injection (2 x 10(9) plaque forming units). Pit-1 activated hepatic expression of the endogenous prolactin (PRL), GH, and TSHbeta genes along with several other markers of lactotrope progenitor cells. Focal clusters (0.2-0.5% of liver cells per tissue section) of periportal cells were positive for PRL by immunofluorescent staining. The PRL-producing cells also expressed proliferating cell nuclear antigen as well as the hepatic stem cell markers (c-Kit, Thy1, and cytokeratin 14). These data indicate that Pit-1 induces the transient differentiation of hepatic progenitor cells into PRL-producing cells, providing additional evidence that transcription factors can specify the differentiation pathway of adult stem cells.
Lee
Eun Jig
EJ
Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611-2908, USA.
Russell
Theron
T
Hurley
Lisa
L
Jameson
J Larry
JL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D010907:Pituitary Hormones / Q000235:genetics; D011388:Prolactin / Q000096:biosynthesis*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000378:metabolism*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D010907:Pituitary Hormones; D011388:Prolactin; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat