Journal of the American Society of Nephrology
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Published ahead of print on September 17, 2009
J Am Soc Nephrol 20: 2315-2327, 2009
© 2009 American Society of Nephrology
doi: 10.1681/ASN.2008111203

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BASIC RESEARCH

Proliferation and Migration of Label-Retaining Cells of the Kidney Papilla

Juan A. Oliver*, Apostolos Klinakis{dagger}, Faisal H. Cheema{ddagger}, Jonathan Friedlander*, Rosemary V. Sampogna*, Timothy P. Martens{ddagger}, Charles Liu*, Argiris Efstratiadis{dagger} and Qais Al-Awqati*

Departments of *Medicine,
{dagger}Genetics and Development, and
{ddagger}Surgery, Columbia University, New York, New York

Correspondence: Dr. Juan A. Oliver, Columbia University, Department of Medicine, 630 West 168th Street, New York, NY 10032. Phone: 212-305-6938; Fax: 212-305-3475; E-mail: jao7{at}columbia.edu

Received for publication November 24, 2008. Accepted for publication June 17, 2009.

The kidney papilla contains a population of cells with several characteristics of adult stem cells, including the retention of proliferation markers during long chase periods (i.e., they are label-retaining cells [LRCs]). To determine whether the papillary LRCs generate new cells in the normal adult kidney, we examined cell proliferation throughout the kidney and found that the upper papilla is a site of enhanced cell cycling. Using genetically modified mice that conditionally expressed green fluorescence protein fused to histone 2B, we observed that the LRCs of the papilla proliferated only in its upper part, where they associate with "chains" of cycling cells. The papillary LRCs decreased in number with age, suggesting that the cells migrated to the upper papilla before entering the cell cycle. To test this directly, we marked papillary cells with vital dyes in vivo and found that some cells in the kidney papilla, including LRCs, migrated toward other parts of the kidney. Acute kidney injury enhanced both cell migration and proliferation. These results suggest that during normal homeostasis, LRCs of the kidney papilla (or their immediate progeny) migrate to the upper papilla and form a compartment of rapidly proliferating cells, which may play a role in repair after ischemic injury.


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J. Am. Soc. Nephrol.Home page
B. D. Humphreys
Slow-Cycling Cells in Renal Papilla: Stem Cells Awaken?
J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2277 - 2279.
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