TY - JOUR
T1 - Genetic tracing of the epithelial lineage during mammalian kidney repair
AU - Humphreys, Benjamin D.
PY - 2011/9
Y1 - 2011/9
N2 - Developing new therapeutic approaches to treat acute kidney injury requires a detailed understanding of endogenous cellular repair. Genetic fate mapping defines cellular hierarchies in vivo and we used this technique to assess a possible contribution of non-epithelial stem cells to renal repair after ischemic injury. Mice with efficient labeling of renal epithelial cells, but not non-epithelial interstitial cells, were subjected to a single cycle or sequential cycles of kidney injury and repair. No dilution of the epithelial cell fate marker was observed despite robust epithelial cell proliferation. Thus, non-tubular cells do not have the ability to migrate across the basement membrane and differentiate into epithelial cells in this model. Instead, surviving tubular epithelial cells are responsible for repair of the damaged nephron. Future studies will need to distinguish between uniform dedifferentiation and proliferation of all epithelial cells after injury versus selective expansion of an intratubular epithelial stem cell.
AB - Developing new therapeutic approaches to treat acute kidney injury requires a detailed understanding of endogenous cellular repair. Genetic fate mapping defines cellular hierarchies in vivo and we used this technique to assess a possible contribution of non-epithelial stem cells to renal repair after ischemic injury. Mice with efficient labeling of renal epithelial cells, but not non-epithelial interstitial cells, were subjected to a single cycle or sequential cycles of kidney injury and repair. No dilution of the epithelial cell fate marker was observed despite robust epithelial cell proliferation. Thus, non-tubular cells do not have the ability to migrate across the basement membrane and differentiate into epithelial cells in this model. Instead, surviving tubular epithelial cells are responsible for repair of the damaged nephron. Future studies will need to distinguish between uniform dedifferentiation and proliferation of all epithelial cells after injury versus selective expansion of an intratubular epithelial stem cell.
KW - acute kidney injury
KW - proliferation
KW - stem cell
UR - http://www.scopus.com/inward/record.url?scp=83655185988&partnerID=8YFLogxK
U2 - 10.1038/kisup.2011.19
DO - 10.1038/kisup.2011.19
M3 - Review article
C2 - 25018906
AN - SCOPUS:83655185988
SN - 2157-1724
VL - 1
SP - 83
EP - 86
JO - Kidney International Supplements
JF - Kidney International Supplements
IS - 3
ER -