The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy
The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy
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DOI：
10.1016/j.ydbio.2006.02.043
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发表时间：
2006-05-15
影响因子：
2.7
通讯作者：
Hennighausen, Lothar
中科院分区：
文献类型：
--
作者：
Buono, Krista D.;Robinson, Gertraud W.;Hennighausen, Lothar
乳腺肺泡由腔（分泌）和基底（肌上皮）细胞组成，它们是共同干细胞的后代。本研究探讨了RBP-J依赖性Notch信号在妊娠期间肺泡形成、维持和细胞组成中的作用。为此目的，使用Cre介导的重组在小鼠的乳腺祖细胞中缺失编码RBP-J（Notch受体的共享转录介质）和Pofut 1（Notch受体活性所需的岩藻糖基转移酶）的基因。RBP-J和Pofut 1的缺失导致基底细胞簇的积累，其特征在于妊娠期间细胞角蛋白（K5）和K14以及平滑肌肌动蛋白（SMA）的存在。激素刺激的突变组织诱导的基底细胞转录因子p63在腔细胞和过度增殖的基底细胞的表达。在激素治疗后观察到K6阳性管腔细胞的瞬时富集，表明在转分化和扩增为基底细胞之前的不成熟阶段暂时停滞。尽管在怀孕期间RBP-J无效的基底细胞的广泛增殖，在退化过程中的激素撤退导致完全重塑和恢复正常的组织结构。我们认为Notch-RBP-J通路通过维持管腔细胞的命运和防止基底细胞不受控制的增殖来调节妊娠期间的肺泡发育。(c)2006爱思唯尔公司All rights reserved.
Mammary alveoli are composed of luminal (secretory) and basal (myoepithelial) cells, which are descendants of a common stem cell. This study addressed the role of RBP-J-dependent Notch signaling in the formation, maintenance and cellular composition of alveoli during pregnancy. For this purpose, tire genes encoding RBP-J, the shared transcriptional mediator of Notch receptors, and Pofut1, a fucosyltransferase required for the activity of Notch receptors, were deleted in mammary progenitor cells in the mouse using Cre-mediated recombination. Loss of RBP-J and Pofut1 led to an accumulation of basal cell clusters characterized by the presence of cytokeratins (K5) and K14 and smooth muscle actin (SMA) during pregnancy. Hormonal stimulation of mutant tissue induced the expression of the basal cell transcription factor p63 in luminal cells and excessive proliferation of basal cells. A transient enrichment of K6-positive luminal cells was observed upon hormonal treatment suggesting a temporary arrest at an immature stage prior to transdifferentiation and expansion as basal cells. Despite the extensive proliferation of RBP-J-null basal cells during pregnancy, hormonal withdrawal during involution resulted in complete remodeling and the restoration of normal tissue architecture. We propose that the Notch-RBP-J pathway regulates alveolar development during pregnancy by maintaining luminal cell fate and preventing uncontrolled basal cell proliferation. (c) 2006 Elsevier Inc. All rights reserved.