TY - JOUR
T1 - Lgr5-Expressing Cells Are Sufficient And Necessary for Postnatal Mammary Gland Organogenesis
AU - Plaks, Vicki
AU - Brenot, Audrey
AU - Lawson, Devon A.
AU - Linnemann, Jelena R.
AU - Van Kappel, Eline C.
AU - Wong, Karren C.
AU - de Sauvage, Frederic
AU - Klein, Ophir D.
AU - Werb, Zena
N1 - Funding Information:
We thank Dr. Nirav Bhakta for help with the single-cell PCR analysis, Drs. Brian Biehs and Hua Tian for initial help with the Lgr5 -DTR:GFP breeding, Dr. Roland Wedlich-Soeldner for providing the LifeAct-RFP mice, Michael Kissner for assistance with flow cytometry, Ying Yu and Elena Atamaniuc for mice husbandry and genotyping, and Joanne Dai for technical help. This work was supported by grants from the National Cancer Institute, the National Institute of Environmental Health Sciences, and the National Institute of Dental and Craniofacial Research (R01 CA057621 and U01 ES019458 to Z.W. and R01-DE021420 to O.D.K.), by Department of Defense postdoctoral fellowships to V.P. (W81XWH-11-01-0139) and to D.A.L. (W81XWH-11-1-0742), and the Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science (to V.P.). F.d.S. is an employee of Genentech, Inc., and owns shares at Roche.
PY - 2013/1/31
Y1 - 2013/1/31
N2 - Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5+) mammary epithelial cells (MECs). We found that Lgr5+ cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5+ cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.
AB - Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5+) mammary epithelial cells (MECs). We found that Lgr5+ cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5+ cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84873131410&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2012.12.017
DO - 10.1016/j.celrep.2012.12.017
M3 - Article
C2 - 23352663
AN - SCOPUS:84873131410
SN - 2211-1247
VL - 3
SP - 70
EP - 78
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -