Reactivation of NCAM1 defines a subpopulation of human adult kidney epithelial cells with clonogenic and stem/progenitor properties

Ella Buzhor, Dorit Omer, Orit Harari-Steinberg, Zohar Dotan, Einav Vax, Sara Pri-Chen, Sally Metsuyanim, Oren Pleniceanu, Ronald S. Goldstein, Benjamin Dekel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The nephron is composed of a monolayer of epithelial cells that make up its various compartments. In development, these cells begin as mesenchyme. NCAM1, abundant in the mesenchyme and early nephron lineage, ceases to express in mature kidney epithelia. We show that, once placed in culture and released from quiescence, adult human kidney epithelial cells (hKEpCs), uniformly positive for CD24/CD133, re-express NCAM1 in a specific cell subset that attains a stem/progenitor state. Immunosorted NCAM1+ cells overexpressed early nephron progenitor markers (PAX2, SALL1, SIX2, WT1) and acquired a mesenchymal fate, indicated by high vimentim and reduced E-cadherin levels. Gene expression and microarray analysis disclosed both a proximal tubular origin of these cells and molecules regulating epithelial-mesenchymal transition. NCAM1+ cells generated clonal progeny when cultured in the presence of fetal kidney conditioned medium, differentiated along mesenchymal lineages but retained the unique propensity to generate epithelial kidney spheres and produce epithelial renal tissue on single-cell grafting in chick CAM and mouse. Depletion of NCAM1+ cells from hKEpCs abrogated stemness traits in vitro. Eliminating these cells during the regenerative response that follows glycerol-induced acute tubular necrosis worsened peak renal injury in vivo. Thus, higher clone-forming and developmental capacities characterize a distinct subset of adult kidney-derived cells. The ability to influence an endogenous regenerative response via NCAM1 targeting may lead to novel therapeutics for renal diseases.

Original languageEnglish
Pages (from-to)1621-1633
Number of pages13
JournalAmerican Journal of Pathology
Issue number5
StatePublished - Nov 2013


FundersFunder number
Sackler School of Medicine, Tel Aviv University
Israel Science Foundation1139/07
Israel Ministry of Industry
Tel Aviv University


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