title: Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence.
abstract: Understanding how distinct cell types arise from multipotent progenitor cells is a major quest in stem cell biology. The liver and pancreas share many aspects of their early development and possibly originate from a common progenitor. However, how liver and pancreas cells diverge from a common endoderm progenitor population and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we defined the molecular identity of liver and pancreas progenitors that were isolated from the mouse embryo at two time points, spanning the period when the lineage decision is made. The integration of temporal and spatial gene expression profiles unveiled mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the noncanonical Wnt pathway as a potential developmental regulator of this fate decision and capable of inducing the pancreas program in endoderm and liver cells. Our study offers an unprecedented view of gene expression programs in liver and pancreas progenitors and forms the basis for formulating lineage-reprogramming strategies to convert adult hepatic cells into pancreatic cells.
authors.affiliation: Laboratory of Molecular and Cellular Basis of Embryonic Development.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rodríguez-Seguel
authors.forename: Nancy
authors.initials: N
authors.lastname: Mah
authors.forename: Heike
authors.initials: H
authors.lastname: Naumann
authors.forename: Igor M
authors.initials: IM
authors.lastname: Pongrac
authors.forename: Nuria
authors.initials: N
authors.lastname: Cerdá-Esteban
authors.forename: Jean-Fred
authors.initials: JF
authors.lastname: Fontaine
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Andrade-Navarro
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Spagnoli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D004707:Endoderm / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000196:embryology; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000196:embryology
chemical_list: D051153:Wnt Proteins
keywords: RNA-seq; Wnt signaling; liver; mouse; pancreas