Institute of Animal Science, Agricultural Research Organization (ARO), The Volcani Center, Bet-Dagan, Israel; The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel.
Institute of Animal Science, Agricultural Research Organization (ARO), The Volcani Center, Bet-Dagan, Israel.
Exp Cell Res. 2019 Sep 15;382(2):111477. doi: 10.1016/j.yexcr.2019.06.022. Epub 2019 Jun 23.
Expansion of the mammary epithelial stem cell pool holds promise for consequent mammary gland development and production. Complementary analyses of bovine mammary implants maintained in de-epithelialized mouse mammary fat pad and endogenous mouse mammary gland were performed to elucidate the effect of calorie restriction (CR) on stem cell self-renewal. CR elevated propagation rate and non-adherent mammosphere generation in cultured bovine mammary cells. A corresponding decrease in progenitor-induced colony formation and differentiation marker expression was noted. In the mouse gland, CR enhanced the take rate of transplanted cells and outgrowths' fat pad occupancy. Downregulating mTOR activity by rapamycin administration reproduced CR's effects on stem cell self-renewal within a shorter period. Flow cytometry demonstrated a significant 1.5-fold increase in stem cell number and a corresponding decrease in luminal progenitor and differentiated cells. Consequent effects of rapamycin administration included enhanced ductlet generation in bovine implants and higher milk-protein gene expression in cultured mouse mammary cells. The stimulatory effect of CR on BST-1 expression in both bovine implants and mouse glands resembled that noted in the intestinal Paneth stem cell niche (Yilmaz et al., 2012). A putative niche may also exist in the mammary gland, conveying energy-status information to the insulated stem cells.
扩大乳腺上皮干细胞池有望促进乳腺发育和产奶。本研究通过对去上皮化的小鼠乳腺脂肪垫内的牛乳腺植入物和内源性小鼠乳腺进行互补分析，阐明了热量限制（CR）对干细胞自我更新的影响。CR 提高了培养的牛乳腺细胞的增殖率和非贴壁类乳腺球体的生成。同时，祖细胞诱导的集落形成和分化标志物的表达减少。在小鼠乳腺中，CR 提高了移植细胞的植入率和生长部位的脂肪垫占有率。雷帕霉素通过下调 mTOR 活性复制了 CR 对干细胞自我更新的影响，且作用时间更短。流式细胞术显示，干细胞数量显著增加了 1.5 倍，同时管腔祖细胞和分化细胞相应减少。雷帕霉素给药的后续影响包括增强了牛植入物中的小管生成和培养的小鼠乳腺细胞中的乳蛋白基因表达。CR 对牛植入物和小鼠乳腺中 BST-1 表达的刺激作用与在肠道 Paneth 干细胞龛（Yilmaz 等人，2012）中观察到的相似。乳腺中可能也存在一个龛位，将能量状态信息传递给隔离的干细胞。
