Lgr5-Expressing Cells Are Sufficient and Necessary for Postnatal Mammary Gland Organogenesis

作者: Vicki Plaks , Audrey Brenot , Devon A. Lawson , Jelena R. Linnemann , Eline C. Van Kappel

DOI: 10.1016/J.CELREP.2012.12.017

关键词:

摘要: Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal enriched in Wnt-responsive can reconstitute cleared fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene was identified as major cell marker the small intestine, colon, stomach, hair follicle, well kidney nephrons. Here, we demonstrate outstanding regenerative potential rare population Lgr5-expressing (Lgr5(+)) (MECs). We found that Lgr5(+) reside within basal population, superior other regenerating functional glands (MGs), exceptionally efficient reconstituting MGs from single cells, exhibit capacity serial transplantations. Loss-of-function depletion experiments transplanted MECs or pubertal revealed these not only sufficient but also necessary for organogenesis.

参考文章(48)
Jonathan Z Long, Chantal S Lackan, Anna-Katerina Hadjantonakis, Genetic and spectrally distinct in vivo imaging: embryonic stem cells and mice with widespread expression of a monomeric red fluorescent protein BMC Biotechnology. ,vol. 5, pp. 20- 20 ,(2005) , 10.1186/1472-6750-5-20
Howard A. Bern, Phyllis B. Blair, K. B. DeOme, L. J. Faulkin, Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Research. ,vol. 19, pp. 515- ,(1959)
Karin E de Visser, Metamia Ciampricotti, Ewa M Michalak, David Wei-Min Tan, Ewoud N Speksnijder, Cheei-Sing Hau, Hans Clevers, Nick Barker, Jos Jonkers, Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland. The Journal of Pathology. ,vol. 228, pp. 300- 309 ,(2012) , 10.1002/PATH.4096
Charlotta Lindvall, Nicole C. Evans, Cassandra R. Zylstra, Yi Li, Caroline M. Alexander, Bart O. Williams, The Wnt Signaling Receptor Lrp5 Is Required for Mammary Ductal Stem Cell Activity and Wnt1-induced Tumorigenesis Journal of Biological Chemistry. ,vol. 281, pp. 35081- 35087 ,(2006) , 10.1074/JBC.M607571200
N. Barker, J.H. van Es, V. Jaks, M. Kasper, H. Snippert, R. Toftgard, H. Clevers, Very long-term self-renewal of small intestine, colon, and hair follicles from cycling Lgr5+ve stem cells. Cold Spring Harbor Symposia on Quantitative Biology. ,vol. 73, pp. 351- 356 ,(2008) , 10.1101/SQB.2008.72.003
Mark Shackleton, François Vaillant, Kaylene J. Simpson, John Stingl, Gordon K. Smyth, Marie-Liesse Asselin-Labat, Li Wu, Geoffrey J. Lindeman, Jane E. Visvader, Generation of a functional mammary gland from a single stem cell Nature. ,vol. 439, pp. 84- 88 ,(2006) , 10.1038/NATURE04372
Nick Barker, Johan H. van Es, Jeroen Kuipers, Pekka Kujala, Maaike van den Born, Miranda Cozijnsen, Andrea Haegebarth, Jeroen Korving, Harry Begthel, Peter J. Peters, Hans Clevers, Identification of stem cells in small intestine and colon by marker gene Lgr5 Nature. ,vol. 449, pp. 1003- 1007 ,(2007) , 10.1038/NATURE06196
Wendy A Woodward, Mercy S Chen, Fariba Behbod, Jeffrey M Rosen, On mammary stem cells. Journal of Cell Science. ,vol. 118, pp. 3585- 3594 ,(2005) , 10.1242/JCS.02532
Jimmie E. Fata, Hidetoshi Mori, Andrew J. Ewald, Hui Zhang, Evelyn Yao, Zena Werb, Mina J. Bissell, The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGFα and FGF7 in morphogenesis of mouse mammary epithelium Developmental Biology. ,vol. 306, pp. 193- 207 ,(2007) , 10.1016/J.YDBIO.2007.03.013
Hua Tian, Brian Biehs, Søren Warming, Kevin G. Leong, Linda Rangell, Ophir D. Klein, Frederic J. de Sauvage, A reserve stem cell population in small intestine renders Lgr5 -positive cells dispensable Nature. ,vol. 478, pp. 255- 259 ,(2011) , 10.1038/NATURE10408