title: Pituitary transcription factor-1 induces transient differentiation of adult hepatic stem cells into prolactin-producing cells in vivo.
abstract: 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.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611-2908, USA.
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.forename: Theron
authors.initials: T
authors.lastname: Russell
authors.forename: Lisa
authors.initials: L
authors.lastname: Hurley
authors.forename: J Larry
authors.initials: JL
authors.lastname: Jameson
mesh_terms: 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*
chemical_list: 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