title: Novel pancreas organogenesis markers refine the pancreatic differentiation roadmap of embryonic stem cells.
abstract: The generation of pancreatic endocrine and exocrine functional precursors from embryonic stem cells (ESCs) is an intriguing opportunity to address cell therapy challenges. The main goal of cellular regeneration is to derive, in vitro, pancreatic progenitor cells (PPCs) that retain the capacity to differentiate following the in vivo developmental ontogeny. In our work, we aim to refine the pancreatic in vitro cellular transitions, through the identification of the intrinsic factors that mark the pancreas budding process at embryonic stage 10.5 (E10.5), in which pancreas precursor specification predominantly occurs. We identified a cohort of genes (Bex1, Nepn, Pcbd1, Prdxdd1, Rnf160, Slc2a1, and Tff3) that marked the pancreas budding genesis, and above all signaled ESC differentiation transitions during pancreatic lineage commitment. Noticeably, we demonstrated that the expression of Nepn marked a naïve pancreatic cellular state that resembled PPC-like specification. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment.
authors.affiliation: Biogem, Istituto di Ricerche Genetiche Gaetano Salvatore, Ariano Irpino, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: De Angelis
authors.forename: Filomena
authors.initials: F
authors.lastname: Russo
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Angelo
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.forename: Marica
authors.initials: M
authors.lastname: Gemei
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Mario
authors.initials: M
authors.lastname: De Felice
authors.forename: Geppino
authors.initials: G
authors.lastname: Falco
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000502:physiology*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009928:Organ Specificity; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: C118512:Bex1 protein, mouse; D015415:Biomarkers; D006023:Glycoproteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C515971:nephrocan protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein