title: Reconstituting pancreas development from purified progenitor cells reveals genes essential for islet differentiation.
abstract: Developmental biology is challenged to reveal the function of numerous candidate genes implicated by recent genome-scale studies as regulators of organ development and diseases. Recapitulating organogenesis from purified progenitor cells that can be genetically manipulated would provide powerful opportunities to dissect such gene functions. Here we describe systems for reconstructing pancreas development, including islet β-cell and α-cell differentiation, from single fetal progenitor cells. A strict requirement for native genetic regulators of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the authenticity of differentiation programs in vitro. Efficient genetic screens permitted by this system revealed that Prdm16 is required for pancreatic islet development in vivo. Discovering the function of genes regulating pancreas development with our system should enrich strategies for regenerating islets for treating diabetes mellitus.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Cecil M
authors.initials: CM
authors.lastname: Benitez
authors.forename: Amar
authors.initials: A
authors.lastname: Ghodasara
authors.forename: Lucy
authors.initials: L
authors.lastname: Liu
authors.forename: Graeme W
authors.initials: GW
authors.lastname: McLean
authors.forename: Jonghyeob
authors.initials: J
authors.lastname: Lee
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Blauwkamp
authors.forename: Roeland
authors.initials: R
authors.lastname: Nusse
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Gu
authors.forename: Seung K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003920:Diabetes Mellitus / Q000378:metabolism / Q000628:therapy; D005260:Female; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C469265:ARX protein, mouse; C407737:Neurog3 protein, mouse; C110218:Pax4 protein, mouse; C521133:Prdm16 protein, mouse
keywords: endocrine; exocrine; insulin; stem cell; transcription factor