title: Evidence for a common progenitor of epithelial and mesenchymal components of the liver.
abstract: Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. the liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Conigliaro
authors.forename: L
authors.initials: L
authors.lastname: Amicone
authors.forename: V
authors.initials: V
authors.lastname: Costa
authors.forename: M
authors.initials: M
authors.lastname: De Santis Puzzonia
authors.forename: C
authors.initials: C
authors.lastname: Mancone
authors.forename: B
authors.initials: B
authors.lastname: Sacchetti
authors.forename: C
authors.initials: C
authors.lastname: Cicchini
authors.forename: F
authors.initials: F
authors.lastname: Garibaldi
authors.forename: D A
authors.initials: DA
authors.lastname: Brenner
authors.forename: T
authors.initials: T
authors.lastname: Kisseleva
authors.forename: P
authors.initials: P
authors.lastname: Bianco
authors.forename: M
authors.initials: M
authors.lastname: Tripodi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D003893:Desmin / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D003893:Desmin; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse