PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool
PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool
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DOI：
10.1073/pnas.0807640106
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发表时间：
2009-03-24
影响因子：
11.1
通讯作者：
Watson, Christine J.
中科院分区：
文献类型：
--
作者：
Li, Wenjing;Ferguson, Brian J.;Watson, Christine J.
早幼粒细胞白血病蛋白（PML）的核结构域在许多细胞过程中作为信号节点。虽然PML表达在驱动受损细胞的细胞命运决定中的影响已经得到了很好的确立，但PML在组织发育背景下的功能还不太清楚。在此，研究了PML在小鼠乳腺发育过程中的体内作用。数据显示，PML的表达是由三个成员的转录因子，精心策划的功能发育的乳腺分泌上皮细胞在怀孕期间的Stat家庭的紧密调控。发育表型也发现在处女和怀孕的Pml无效小鼠，典型的乳腺上皮细胞的异常分化减少导管和肺泡的发展。还发现PML耗竭扰乱两种不同管腔祖细胞群体的平衡。总体而言，它表明，PML是所需的双能管腔祖细胞的细胞谱系确定和PML表达的精确调节是肺泡细胞的功能分化所需的。
Nuclear domains of promyelocytic leukemia protein (PML) are known to act as signaling nodes in many cellular processes. Although the impact of PML expression in driving cell fate decisions for injured cells is well established, the function of PML in the context of tissue development is less well understood. Here, the in vivo role of PML in developmental processes in the murine mammary gland has been investigated. Data are presented showing that expression of PML is tightly regulated by three members of the Stat family of transcription factors that orchestrate the functional development of the mammary secretory epithelium during pregnancy. Developmental phenotypes were also discovered in the virgin and pregnant Pml null mouse, typified by aberrant differentiation of mammary epithelia with reduced ductal and alveolar development. PML depletion was also found to disturb the balance of two distinct luminal progenitor populations. Overall, it is shown that PML is required for cell lineage determination in bi-potent luminal progenitor cells and that the precise regulation of PML expression is required for functional differentiation of alveolar cells.