A Subpopulation of Label-Retaining Cells of the Kidney Papilla Regenerates Injured Kidney Medullary Tubules.
To determine whether adult kidney papillary label-retaining cells (pLRCs) are specialized precursors, we analyzed their transcription profile. Among genes overexpressed in pLRCs, we selected candidate genes to perform qPCR and immunodetection of their encoded proteins. We found that Zfyve27, which encodes protrudin, identified a subpopulation of pLRCs. With Zfyve27-CreERT2 transgenic and reporter mice we generated bitransgenic animals and performed cell-lineage analysis. Post tamoxifen, Zfyve27-CreERT2 marked cells preferentially located in the upper part of the papilla. These cells were low cycling and did not generate progeny even after long-term observation, thus they did not appear to contribute to kidney homeostasis. However, after kidney injury, but only if severe, they activated a program of proliferation, migration, and morphogenesis generating multiple and long tubular segments. Remarkably these regenerated tubules were located preferentially in the kidney medulla, indicating that repair of injury in the kidney is regionally specified. These results suggest that different parts of the kidney have different progenitor cell pools.
Department of Medicine, Columbia University, New York, NY 10032, USA. Electronic address: jao7@columbia.edu.
Juan A
JA
Oliver
Department of Medicine, Columbia University, New York, NY 10032, USA.
Rosemary V
RV
Sampogna
Department of Medicine, Columbia University, New York, NY 10032, USA.
Sumreen
S
Jalal
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Qing-Yin
QY
Zhang
Department of Medicine, Columbia University, New York, NY 10032, USA.
Alexander
A
Dahan
Department of Medicine, Columbia University, New York, NY 10032, USA.
Weiwei
W
Wang
Department of Medicine, Columbia University, New York, NY 10032, USA.
Tian Huai
TH
Shen
Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: qa1@columbia.edu.
Qais
Q
Al-Awqati
D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D007679:Kidney Medulla / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D012038:Regeneration / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
D033921:Vesicular Transport Proteins; C514783:protrudin protein, mouse; D013629:Tamoxifen