Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science. 2017 Apr 21;356(6335). doi: 10.1126/science.aal3485. Epub 2017 Mar 9.
The stem cell niche is a complex local signaling microenvironment that sustains stem cell activity during organ maintenance and regeneration. The mammary gland niche must support its associated stem cells while also responding to systemic hormonal regulation that triggers pubertal changes. We find that , the major Hedgehog pathway transcriptional effector, acts within mouse mammary stromal cells to direct a hormone-responsive niche signaling program by activating expression of factors that regulate epithelial stem cells as well as receptors for the mammatrophic hormones estrogen and growth hormone. Whereas prior studies implicate stem cell defects in human disease, this work shows that niche dysfunction may also cause disease, with possible relevance for human disorders and in particular the breast growth pathogenesis associated with combined pituitary hormone deficiency.
干细胞龛是一个复杂的局部信号微环境，在器官维持和再生过程中维持干细胞的活性。乳腺龛必须在支持其相关干细胞的同时，对触发青春期变化的全身激素调节做出反应。我们发现，主要的 Hedgehog 通路转录效应因子，在小鼠乳腺基质细胞中发挥作用，通过激活调节上皮干细胞以及催乳激素雌激素和生长激素受体的因子的表达，来指导激素反应性龛信号程序。虽然先前的研究表明人类疾病中的干细胞缺陷，但这项工作表明，龛功能障碍也可能导致疾病，这可能与人类疾病有关，特别是与联合垂体激素缺乏症相关的乳腺生长发病机制有关。
