Journal ArticleDOI
Purification and unique properties of mammary epithelial stem cells
John Stingl,Peter Eirew,Ian Ricketson,Mark Shackleton,François Vaillant,David H. Choi,Haiyan I. Li,Connie J. Eaves,Connie J. Eaves +8 more
TLDR
The use of multi-parameter cell sorting and limiting dilution transplant analysis is reported to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions.Abstract:
Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.read more
Citations
More filters
Journal ArticleDOI
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
Journal ArticleDOI
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
Toshiro Sato,Robert G.J. Vries,Hugo J. Snippert,Marc van de Wetering,Nick Barker,Daniel E. Stange,Johan H. van Es,Arie Abo,Pekka Kujala,Peter J. Peters,Hans Clevers +10 more
TL;DR: It is concluded that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
Journal ArticleDOI
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
Christophe Ginestier,Min Hee Hur,Emmanuelle Charafe-Jauffret,Florence Monville,Julie Dutcher,Marty Brown,Jocelyne Jacquemier,Patrice Viens,Celina G. Kleer,Suling Liu,Anne F. Schott,Daniel F. Hayes,Daniel Birnbaum,Max S. Wicha,Gabriela Dontu +14 more
TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
Journal ArticleDOI
Association of reactive oxygen species levels and radioresistance in cancer stem cells
Maximilian Diehn,Robert W. Cho,Neethan A. Lobo,Tomer Kalisky,Mary Jo Dorie,Angela N. Kulp,Dalong Qian,Jessica Lam,Laurie Ailles,Manzhi Wong,Benzion Joshua,Michael J. Kaplan,Irene Wapnir,Frederick M. Dirbas,George Somlo,Carlos A. Garberoglio,Benjamin Paz,Jeannie Shen,Sean K. Lau,Stephen R. Quake,J. Martin Brown,Irving L. Weissman,Michael F. Clarke +22 more
TL;DR: It is shown that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells, and subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.
Journal ArticleDOI
Generation of a functional mammary gland from a single stem cell
Mark Shackleton,Mark Shackleton,François Vaillant,François Vaillant,Kaylene J. Simpson,Kaylene J. Simpson,John Stingl,Gordon K. Smyth,Marie Liesse Asselin-Labat,Marie Liesse Asselin-Labat,Li Wu,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Jane E. Visvader,Jane E. Visvader +14 more
TL;DR: It is shown that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo and establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.
References
More filters
Journal ArticleDOI
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
TL;DR: It is discovered that display of Hoechst fluorescence simultaneously at two emission wavelengths revealed a small and distinct subset of whole bone marrow cells that had phenotypic markers of multipotential HSC, which were shown in competitive repopulation experiments to contain the vast majority of HSC activity from murine bone marrow and to be enriched at least 1,000-fold for in vivo reconstitution activity.
Journal ArticleDOI
In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells
Gabriela Dontu,Wissam M. Abdallah,Jessica M. Foley,Kyle W. Jackson,Michael F. Clarke,Mari J. Kawamura,Max S. Wicha +6 more
TL;DR: It is demonstrated that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems.
Journal ArticleDOI
The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype
Sheng Zhou,John D. Schuetz,Kevin D. Bunting,Anne-Marie Colapietro,Janardhan Sampath,John J. Morris,Irina Lagutina,Gerard Grosveld,Mitsujiro Osawa,Hiromitsu Nakauchi,Brian P. Sorrentino +10 more
TL;DR: Results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.
Journal ArticleDOI
Generation of a functional mammary gland from a single stem cell
Mark Shackleton,Mark Shackleton,François Vaillant,François Vaillant,Kaylene J. Simpson,Kaylene J. Simpson,John Stingl,Gordon K. Smyth,Marie Liesse Asselin-Labat,Marie Liesse Asselin-Labat,Li Wu,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Jane E. Visvader,Jane E. Visvader +14 more
TL;DR: It is shown that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo and establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.
Journal Article
Generation of a functional mammary gland from a single stem cell
Mark Shackleton,François Vaillant,Kaylene J. Simpson,John Stingl,Gordon K. Smyth,Marie Liesse Asselin-Labat,Li Wu,Jane E. Visvader,Geoffrey J. Lindeman +8 more
TL;DR: In this article, the mammary gland can be functionally regenerated in mice by serial transplantation of epithelial fragments, providing evidence for the existence of self-renewing, multipotential mammary stem cells (MaSCs).
Related Papers (5)
Generation of a functional mammary gland from a single stem cell
Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers
Elgene Lim,Elgene Lim,François Vaillant,Di Wu,Di Wu,Natasha C. Forrest,Bhupinder Pal,Adam H. Hart,Marie Liesse Asselin-Labat,David E. Gyorki,David E. Gyorki,Teresa Ward,Audrey Partanen,Frank Feleppa,Lily I. Huschtscha,Heather Thorne,Stephen B. Fox,Max Yan,Juliet D. French,Melissa A. Brown,Gordon K. Smyth,Jane E. Visvader,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Geoffrey J. Lindeman +24 more