Parity-induced mammary epithelial cells are multipotent and express cell surface markers associated with stem cells.
Parity-induced mammary epithelial cells (PI-MECs) are defined as a pregnancy hormone-responsive cell population that activates the promoter of late milk protein genes during the second half of pregnancy and lactation. However, unlike their terminally differentiated counterparts, these cells do not undergo programmed cell death during post-lactational remodeling of the gland. We previously demonstrated that upon transplantation into an epithelial-free mammary fat pad, PI-MECs exhibited two important features of multipotent mammary epithelial progenitors: a) self-renewal, and b) contribution to ductal and alveolar morphogenesis. In this new report, we introduce a new method to viably label PI-MECs. Using this methodology, we analyzed the requirement of ovarian hormones for the maintenance of this epithelial subtype in the involuted mammary gland. Furthermore, we examined the expression of putative stem cell markers and found that a portion of GFP-labeled PI-MECs were part of the CD24(+)/CD49f(high) mammary epithelial subtype, which has recently been suggested to contain multipotent stem cells. Subsequently, we demonstrated that isolated PI-MECs were able to form mammospheres in culture, and upon transplantation, these purified epithelial cells were capable of establishing a fully functional mammary gland. These observations suggest that PI-MECs contain multipotent progenitors that are able to self renew and generate diverse epithelial lineages present in the murine mammary gland.
Matulka
Laurice A
LA
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Rm. 8009, Omaha, NE 68198-6805, USA.
Triplett
Aleata A
AA
Wagner
Kay-Uwe
KU
D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D039503:Integrin alpha6 / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010298:Parity; D011247:Pregnancy; D033581:Stem Cell Transplantation; D019076:Transgenes / Q000235:genetics
D051927:CD24 Antigen; D012739:Gonadal Steroid Hormones; D039503:Integrin alpha6; D049452:Green Fluorescent Proteins