Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool
Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool
复制标题
腊肠犬的耗竭会扰乱乳腺发育并改变乳腺祖细胞库的组成
DOI：
10.1016/j.stemcr.2018.11.010
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发表时间：
2019-01-08
影响因子：
5.9
通讯作者：
Pestell, Richard G.
中科院分区：
文献类型：
--
作者：
Jiao, Xuanmao;Li, Zhiping;Pestell, Richard G.
DACH 1丰度在人类恶性肿瘤中减少，包括乳腺癌。在此，在胚胎中的多能胎儿乳腺干细胞、混合谱系前体细胞以及成体基底细胞和（ER α（+））腔祖细胞中检测到DACH 1。在转基因小鼠中，6周时Dachl基因缺失减少了导管分支，减少了乳腺基底细胞（Lin（-）CD 24（中）CD 29（高））的比例，并减少了基底细胞角蛋白5的丰度，而DACHl过表达诱导了导管分支，增加了Gata 3和Notchl，并扩大了LA-7乳腺细胞中的乳腺球形成。乳腺转化生长因子β（TGF-β）活性，已知减少导管分支和减少基底细胞群，在Dachl缺失后增加，与SMAD磷酸化增加相关。内源性DACH 1降低了用于受体活化的支架蛋白Smad锚与促进TGF-β活化的Smad 2/3的关联。DACH 1在体内增加基底细胞，增强导管形成并抑制TGF-β活性。
DACH1 abundance is reduced in human malignancies, including breast cancer. Herein DACH1 was detected among multipotent fetal mammary stem cells in the embryo, among mixed lineage precursors, and in adult basal cells and (ER alpha(+)) luminal progenitors. Dachl gene deletion at 6 weeks in transgenic mice reduced ductal branching, reduced the proportion of mammary basal cells (Lin(-) CD24(med) CD29(high)) and reduced abundance of basal cytokeratin 5, whereas DACH1 overexpression induced ductal branching, increased Gata3 and Notchl, and expanded mammosphere formation in LA-7 breast cells. Mammary gland-transforming growth factor beta (TGF-beta) activity, known to reduce ductal branching and to reduce the basal cell population, increased upon Dachl deletion, associated with increased SMAD phosphorylation. Association of the scaffold protein Smad anchor for receptor activation with Smad2/3, which facilitates TGF-beta activation, was reduced by endogenous DACH1. DACH1 increases basal cells, enhances ductal formation and restrains TGF-beta activity in vivo.