Macrophage-secreted CSF1 transmits a calorie restriction self-renewing signal to mammary epithelial stem cells

Calorie restriction (CR) enhances stem cell self-renewal in various tissues, including the mammary gland. The hypothesis propelling this study states that similarly to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in the energy supply and, for that matter, depend on signals from a specific niche. Combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the CR inducing effect on mammary stem cell self-renewal. Overall design: The niche that transmits the calorie restriction (CR) self-renewing signal was identified by exposing stem cell cultures to conditioned medium collected from individual cell populations of CR and their ad libitum-fed counterparts. The signaling molecule was identified by RNA-Seq of the identified non-epithelial cell population. Conformation studies were then ensued.