Conversion of Terminally Differentiated Cells to Progenitor Cells-A Trial of Tissue Regeneration Not by Targeting Stem Cells

p53和RB肿瘤抑制因子调控的通路在终末分化细胞的分化和不可逆的细胞周期阻滞中发挥重要作用。为了诱导终末分化细胞的去分化和增殖，我们研究了DRIL1及其密切相关的DRIL2 （ARID(AT-rich interaction domain) dna结合蛋白家族成员）在这些主要肿瘤抑制通路中的功能作用。我们发现DRIL1与p53协同激活pro-arrest p21^WAF1转录，DRIL1和DRIL2在e2f靶基因表达和细胞周期进程中发挥重要作用，并且DRIL2的功能是成骨分化所必需的。此外，我们的研究结果表明，除了DRIL1或DRIL2的敲低外，p53和RB功能的抑制是诱导终末分化细胞去分化和增殖的必要条件。这些结果为最终分化细胞向祖细胞的转化提供了重要的见解。

The pathways regulated by p53 and RB tumor suppressors play important roles in differentiation and irreversible cell-cycle arrest in terminally differentiated cells. To induce dedifferentiation and proliferation of terminally differentiated cells, we investigated functional roles of DRIL1 and its closely related DRIL2, family members of ARID(AT-rich interaction domain) DNA-binding proteins, in these major tumor suppressor pathways. We found that DRIL1 cooperates with p53 to activate pro-arrest p21^WAF1 transcription, and that DRIL1 and DRIL2 play important roles in E2F-target gene expression and cell cycle progression, and that DRIL2 function is required for osteogenic differentiation. In addition, our results suggest that, in addition to DRIL1 or DRIL2 knockdown, inhibition of p53 and RB functions is required for inducing dedifferentiation and proliferation of terminally differentiated cells. These results provide important insights to the conversion of terminally differentiated cells into progenitor cells.