Rb regulates fate choice and lineage commitment in vivo.
Rb regulates fate choice and lineage commitment in vivo.
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作者：
Rb-1肿瘤抑制基因突变发生在三分之一的人类肿瘤中，尤其与视网膜母细胞瘤和骨肉瘤有关。许多功能都归因于人类Rb-1基因的产物pRb。最著名的是pRb通过抑制E2F转录因子和转录抑制编码细胞周期调节因子的基因来促进细胞周期退出的能力。此外，体外研究表明，pRb可以调节几种主要的分化诱导剂转录因子。根据分化因子和细胞环境的不同，pRb可以抑制或促进它们的转录活性。例如，pRb与Runx2结合，增强其在体外促进成骨分化程序的能力。相反，pRb和E2F一起作用于抑制PPARγ，PPAR是脂肪形成的主要激活剂。由于成骨细胞和脂肪细胞都可以从间充质干细胞分化而来，这些观察表明pRb可能在这两种命运之间的选择中发挥了作用。然而，到目前为止，还没有活体内证明这一点的证据。在这里，我们使用小鼠模型在间充质组织发育和肿瘤发生的背景下解决这一假说。我们的数据表明，在活体中，Rb状态在决定骨骼和棕色脂肪组织之间的命运选择方面起着关键作用。
Mutation of the RB-1 tumour suppressor occurs in one third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma. Numerous functions have been ascribed to the product of the human RB-1 gene, pRB. The best known is pRB’s ability to promote cell cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell cycle regulators. In addition, pRB has been shown in vitro to regulate several transcription factors that are master differentiation inducers. Depending on the differentiation factor and cellular context, pRB can either suppress or promote their transcriptional activity. For example, pRB binds to Runx2 and potentiates its ability to promote osteogenic differentiation program in vitro. In contrast, pRB acts together with E2F to suppress PPARγ, the master activator of adipogenesis. Since osteoblasts and adipocytes can both arise from mesenchymal stem cells, these observations suggest that pRB might play a role in the choice between these two fates. However, to date, there is no evidence for this in vivo. Here we use mouse models to address this hypothesis in the context of mesenchymal tissue development and tumorigenesis. Our data show that Rb status plays a key role in establishing fate choice between bone and brown adipose tissue in vivo.
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DOI：
10.1073/pnas.0805462105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Berman, Seth D.;Calo, Eliezer;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.
影响因子：
29
作者：
Scimè, A;Grenier, G;Rudnicki, MA
通讯作者：
Rudnicki, MA
DOI：
10.1073/pnas.0611568104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Dali-Youcef, Nassim;Mataki, Chikage;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
30.8
作者：
Jonkers, J;Meuwissen, R;Berns, A
通讯作者：
Berns, A
影响因子：
16
作者：
Thomas, DM;Carty, SA;Hinds, PW
通讯作者：
Hinds, PW