Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-Myc and other stem cell transcription factors.
Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-Myc and other stem cell transcription factors.
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DOI：
10.1038/srep01673
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发表时间：
2013
影响因子：
4.6
通讯作者：
Roberts, David D.
中科院分区：
文献类型：
--
作者：
Kaur, Sukhbir;Soto-Pantoja, David R.;Stein, Erica V.;Liu, Chengyu;Elkahloun, Abdel G.;Pendrak, Michael L.;Nicolae, Alina;Singh, Satya P.;Nie, Zuqin;Levens, David;Isenberg, Jeffrey S.;Roberts, David D.
通过血小板反应蛋白-1受体CD 47的信号传导广泛地限制了细胞和组织的应激存活，但其分子机制尚不完全清楚。我们现在表明，CD 47的损失允许原代小鼠内皮细胞的持续增殖，增加不对称分裂，并使这些细胞自发重编程形成多能胚状体样簇。c-Myc、Klf 4、Oct 4和Sox 2表达在CD 47-null内皮细胞、CD 47-和血小板反应蛋白-1-null小鼠的几种组织以及缺乏CD 47的人T细胞系中升高。CD 47敲低可在细胞内和体内急剧增加c-Myc和其他干细胞转录因子的mRNA水平，而血小板反应蛋白-1连接CD 47可抑制c-Myc表达。增加CD 47水平的抑制作用可以通过维持c-Myc表达来克服，并且在具有失调的c-Myc的细胞中不存在。因此，CD 47拮抗剂通过克服c-Myc和其他干细胞转录因子的负调控而使细胞自我更新和重编程成为可能。
Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors.
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影响因子：
11.2
作者：
Chao MP;Alizadeh AA;Tang C;Jan M;Weissman-Tsukamoto R;Zhao F;Park CY;Weissman IL;Majeti R
通讯作者：
Majeti R
影响因子：
8.8
作者：
Huber, K R;Schmidt, W F;Thompson, E A;Forsthoefel, A M;Neuberg, R W;Ettinger, R S
通讯作者：
Ettinger, R S
DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
4.8
作者：
Kaur, Sukhbir;Kuznetsova, Svetlana A.;Roberts, David D.
通讯作者：
Roberts, David D.
影响因子：
20.1
作者：
Isenberg, Jeff S.;Romeo, Martin J.;Roberts, David D.
通讯作者：
Roberts, David D.