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RESEARCH PRODUCT
Isolation and characterization of a murine resident liver stem cell.
F SiepiMateus T. GuerraMarta CollettiRoberta ZiniAlice ConigliaroCarla CicchiniVeronica BordoniMarco TripodiLaura AmiconeMartina LeopizziRossella Manfredinisubject
Cellular differentiationLiver Stem CellCell SeparationBiologyImmunophenotypingLiver progenitor cellsMiceChondrocyteshepatocyteAnimalsCell LineageProgenitor cellLiver progenitor cells; hepatocyte; differentiationMolecular BiologyCells CulturedMultipotent Stem CellOligonucleotide Array Sequence AnalysisNeuronsOsteoblastsAnimalOligonucleotide Array Sequence AnalysiLiver cellOsteoblastGene Expression ProfilingMultipotent Stem CellsMesenchymal stem cellCell DifferentiationCell BiologydifferentiationNeuronChondrocyteMolecular biologyLiver regenerationCell biologyPhenotypeAnimals NewbornLiverMultipotent Stem CellHepatocytesStem cellAnimals; Animals Newborn; Cell Differentiation; Cell Lineage; Cell Separation; Cells Cultured; Chondrocytes; Gene Expression Profiling; Hepatocytes; Immunophenotyping; Liver; Mice; Multipotent Stem Cells; Neurons; Oligonucleotide Array Sequence Analysis; Osteoblasts; Phenotype; Molecular Biology; Cell Biologydescription
Increasing evidence provides support that mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, biology and their role in liver cell turnover and regeneration remain to be further clarified. In this study, we report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potentiality distinct from other previously described liver precursor/stem cells. RLSCs, derived from fetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alpha-fetoprotein+ and albumin-. This molecular phenotype suggests a non-hematopoietic origin. RLSC transcriptional profile, defined by microArray technology, highlighted the expression of a broad spectrum of 'plasticity-related genes' and 'developmental genes' suggesting a multi-differentiative potentiality. Indeed, RLSCs spontaneously differentiate into hepatocytes and cholangiocytes and, when cultured in appropriate conditions, into mesenchymal and neuro-ectodermal cell lineages such as osteoblasts/osteocytes, chondrocytes, astrocytes and neural cells. RLSC capability to spontaneously differentiate into hepatocytes, the lack of albumin expression and the broad differentiative potentiality locate them in a pre-hepatoblast/liver precursor cells hierarchical position. In conclusion, RLSCs may provide a useful tool to improve liver stem cell knowledge and to assess new therapeutic approaches for liver diseases.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-01-01 | Cell death and differentiation |