Amphiregulin is Dispensable for Redirection of Non-Mammary Cells to a Mammary Stem Cell Fate in vivo

Authors

• AL George
• CA Boulanger
• GH Smith

Abstract

Amphiregulin (AREG) is a member of the epidermal growth factor family and is necessary for mammary epithelial proliferation, terminal end bud formation, and ductal elongation. AREG-/- mice demonstrate impaired mammary development and form only rudimentary ductal trees, however, AREG-/- glands are still capable of undergoing alveologenesis and lactogenesis during pregnancy. Transplantation of AREG-/- cells into cleared mouse mammary fatpads results in a diminished capacity for epithelial growth (~7%) as compared to wildtype cells. Previously we've shown using engraftment studies in athymic mice that wildtype mammary cells are capable of redirecting non-mammary cells, including testicular cells and embryonic neuronal cells, to a mammary cell phenotype leading to their growth and incorporation into mammary ducts. To determine whether AREG signaling was necessary for this redirection, we inoculated cleared fat pads of 3-week-old female mice in a 1:1 ratio of AREG-/- mammary cells with either WapCre/Rosa26LacZ+ testicular cells or GFP+ embryonic neuronal cells. AREG-/- cells were capable of redirecting both non-mammary cell populations to a mammary phenotype as LacZ+ testicular cells or GFP+ neuronal cells could be visualized in theresulting mammary ducts. Transplantation of fragments from these reprogrammed outgrowths into new mammary fatpads divested of epithelium resulted in secondary outgrowths in 6/10 fat pads. Taken together, this demonstrates the self-renewing capacity of these non-mammary cells and their ability to contribute to new progeny to chimeric outgrowths regardless of AREG expression allowing for recapitulation of the mammary stem cell niche by non-mammary stem cells.

Scientific Focus Area: Developmental Biology

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