title: Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo.
abstract: Pericytes are widely believed to function as mesenchymal stem cells (MSCs), multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse. Fluorescence-activated cell sorting (FACS)-purified Tbx18-expressing cells behaved as MSCs in vitro. However, lineage-tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular smooth muscle cells maintained their identity in aging and diverse pathological settings and did not significantly contribute to other cell lineages. These results challenge the current view of endogenous pericytes as multipotent tissue-resident progenitors and suggest that the plasticity observed in vitro or following transplantation in vivo arises from artificial cell manipulations ex vivo.
authors.affiliation: Skaggs School of Pharmacy, University of California at San Diego, La Jolla, CA 92093, USA; Institute for Biomedical Sciences Abel Salazar and GABBA Graduate Program, University of Porto, Porto 4050-313, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Guimarães-Camboa
authors.affiliation: Skaggs School of Pharmacy, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Cattaneo
authors.affiliation: Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: INSERM UMRS 910, Aix-Marseille Université, 13284 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moore-Morris
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Yusu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.affiliation: Skaggs School of Pharmacy, University of California at San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA; Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: syevans@ucsd.edu.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000375:Aging / Q000235:genetics; D019070:Cell Lineage; D002921:Cicatrix / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019426:Integrases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D009928:Organ Specificity; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse; D049452:Green Fluorescent Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta; C045073:Cre recombinase; D019426:Integrases
keywords: lineage tracing; mesenchymal stem cells; mural cells; pericytes