title: Collecting duct-derived cells display mesenchymal stem cell properties and retain selective in vitro and in vivo epithelial capacity.
abstract: We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelial-to-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. To investigate the origin of kidney MSC-like cells, we further examined Hoxb7(+) fractions within the kidney across postnatal development, identifying a neonatal interstitial GFP(lo) (Hoxb7(lo)) population displaying an expression profile intermediate between epithelium and interstitium. Temporal analyses with Wnt4(GCE/+):R26(tdTomato/+) mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia;
authors.forename: Joan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia;
authors.forename: Usukhbayar
authors.initials: U
authors.lastname: Ariunbold
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia;
authors.forename: Norseha
authors.initials: N
authors.lastname: Suhaimi
authors.affiliation: Diamantina Institute, University of Queensland, Woolloongabba, Queensland, Australia; and.
authors.forename: Nana
authors.initials: N
authors.lastname: Sunn
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Jill A
authors.initials: JA
authors.lastname: McMahon
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia; M.Little@uq.edu.au.
authors.forename: Melissa
authors.initials: M
authors.lastname: Little
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D019902:Chondrocytes / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology; D007685:Kidney Tubules, Collecting / Q000166:cytology*; D061985:Madin Darby Canine Kidney Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010011:Osteocytes / Q000166:cytology; D010641:Phenotype
chemical_list: D018398:Homeodomain Proteins; C093253:Hoxb7 protein, mouse; D049452:Green Fluorescent Proteins; D003094:Collagen
keywords: collecting ducts; epithelial-mesenchymalepithelial transition; kidney; mesenchymal stem cells; stem cell