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J Am Soc Nephrol. 2015 Jan;26(1):81-94. doi: 10.1681/ASN.2013050517. Epub 2014 Jun 5.

Collecting duct-derived cells display mesenchymal stem cell properties and retain selective in vitro and in vivo epithelial capacity.

Author information

1
Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia;
2
Diamantina Institute, University of Queensland, Woolloongabba, Queensland, Australia; and.
3
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.
4
Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia; M.Little@uq.edu.au.

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.

KEYWORDS:

collecting ducts; epithelial-mesenchymalepithelial transition; kidney; mesenchymal stem cells; stem cell

PMID:
24904087
PMCID:
PMC4279727
DOI:
10.1681/ASN.2013050517
[Indexed for MEDLINE]
Free PMC Article
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