PMID- 9550724 OWN - NLM STAT- MEDLINE DCOM- 19980707 LR - 20220215 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 125 IP - 10 DP - 1998 May TI - An entire functional mammary gland may comprise the progeny from a single cell. PG - 1921-30 AB - Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional gland when transplanted into an epithelium-free mammary fat pad. Mouse mammary hyperplasias and tumors are clonal dominant populations and probably represent the progeny of a single transformed cell. Our study provides evidence that single multipotent stem cells positioned throughout the mature fully developed mammary gland have the capacity to produce sufficient differentiated progeny to recapitulate an entire functional gland. Our evidence also demonstrates that these stem cells are self-renewing and are found with undiminished capacities in the newly regenerated gland. We have taken advantage of an experimental model where mouse mammary tumor virus infects mammary epithelial cells and inserts a deoxyribonucleic acid copy(ies) of its genome during replication. The insertions occur randomly within the somatic genome. CzechII mice have no endogenous nucleic acid sequence homology with mouse mammary tumor virus; therefore all viral insertions may be detected by Southern analysis provided a sufficient number of cells contain a specific insertional event. Transplantation of random fragments of infected CzechII mammary gland produced clonal-dominant epithelial populations in epithelium-free mammary fat pads. Serial transplantation of pieces of the clonally derived outgrowths produced second generation glands possessing the same viral insertion sites providing evidence for self-renewal of the original stem cell. Limiting dilution studies with cell cultures derived from third generation clonal outgrowths demonstrated that three multipotent but distinct mammary epithelial progenitors were present in clonally derived mammary epithelial populations. Estimation of the potential number of multipotent epithelial cells that may be evolved from an individual mammary-specific stem cell by self-renewal is in the order of 10(12)-10(13). Therefore, one stem cell might easily account for the renewal of mammary epithelium over several transplant generations. FAU - Kordon, E C AU - Kordon EC AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA. FAU - Smith, G H AU - Smith GH LA - eng PT - Journal Article PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (DNA, Viral) SB - IM MH - Animals MH - Cell Division MH - DNA, Viral/analysis MH - Epithelial Cells MH - Female MH - Mammary Glands, Animal/*cytology/transplantation MH - Mammary Tumor Virus, Mouse MH - Mice MH - Proviruses MH - *Stem Cells EDAT- 1998/06/18 00:00 MHDA- 1998/06/18 00:01 CRDT- 1998/06/18 00:00 PHST- 1998/06/18 00:00 [pubmed] PHST- 1998/06/18 00:01 [medline] PHST- 1998/06/18 00:00 [entrez] AID - 10.1242/dev.125.10.1921 [doi] PST - ppublish SO - Development. 1998 May;125(10):1921-30. doi: 10.1242/dev.125.10.1921.