title: A mammary repopulating cell population characterized in mammary anlagen reveals essential mammary stroma for morphogenesis.
abstract: The cells with mammary repopulating capability can achieve mammary gland morphogenesis in a suitable cellular microenvironment. Using cell surface markers of CD24, CD29 and CD49f, mouse mammary repopulating unit (MRU) has been identified in adult mammary epithelium and late embryonic mammary bud epithelium. However, embryonic MRU remains to be fully characterized at earlier mammary anlagen stage. Here we isolated discrete populations of E14.5 mouse mammary anlagen cells. Only Lin(-)CD24(med)CD29(+) cell population was predicted as E14.5 MRU by examining their capacities of forming mammosphere and repopulating cleared mammary fat pad in vivo. However, when we characterized gene expressions of this E14.5 cell population by comparing with adult mouse MRU (Lin(-)CD24(+)CD29(hi)), the gene profiling of these two cell populations exhibited great differences. Real-time PCR and immunostaining assays uncovered that E14.5 Lin(-)CD24(med)CD29(+) cell population was a heterogeneous stroma-enriched cell population. Then, limiting dilutions and single-cell assays also confirmed that E14.5 Lin(-)CD24(med)CD29(+) cell population possessed low proportion of stem cells. In summary, heterogeneous Lin(-)CD24(med)CD29(+) cell population exhibited mammary repopulating ability in E14.5 mammary anlagen, implying that only suitable mammary stroma could enable mammary gland morphogenesis, which relied on the interaction between rare stem cells and microenvironment.
authors: State Key Laboratories for AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China; College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China.
authors: Jiazhe
authors: J
authors: Song
authors: State Key Laboratories for AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China; College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China.
authors: Kai
authors: K
authors: Xue
authors: College of Life Sciences, Peking University, Beijing, PR China.
authors: Ji
authors: J
authors: She
authors: National Animal Genetic Research Center, Beijing, PR China.
authors: Fangrong
authors: F
authors: Ding
authors: National Animal Genetic Research Center, Beijing, PR China.
authors: Song
authors: S
authors: Li
authors: Department of Animal Science, Oklahoma State University, Stillwater, OK, USA.
authors: Rulan
authors: R
authors: Shangguan
authors: State Key Laboratories for AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China.
authors: Yunping
authors: Y
authors: Dai
authors: College of Life Sciences, Peking University, Beijing, PR China.
authors: Liying
authors: L
authors: Du
authors: State Key Laboratories for AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China. Electronic address: ninglcau@cau.edu.cn.
authors: Ning
authors: N
authors: Li
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D019012:Integrin beta1 / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009024:Morphogenesis / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D051927:CD24 Antigen; D019012:Integrin beta1
keywords: Mammary anlagen stage; Mammary gland morphogenesis; Mammary repopulating units (MRU); Mammary stem/progenitor cell; Mammary stroma