Liu Lin, DiGirolamo Carla M, Navarro Paula A A S, Blasco Maria A, Keefe David L
Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University School of Medicine, Providence, RI 02905, USA.
Exp Cell Res. 2004 Mar 10;294(1):1-8. doi: 10.1016/j.yexcr.2003.10.031.
Expression of telomerase activity presumably is involved in maintaining self-replication and the undifferentiated state of stem cells. Adult mouse bone marrow mesenchymal stem cells (mMSCs) are multipotential cells capable of differentiating into a variety of lineage cell types, including adipocytes and chondrocytes. Here we show that the lacking telomerase of mMSC lose multipotency and the capacity to differentiate. Primary cultures of mMSCs were obtained from both telomerase knockout (mTR(-/-)) and wild-type (WT) mice. The MSCs isolated from mTR(-/-) mice failed to differentiate into adipocytes and chondrocytes, even at early passages, whereas WT MSCs were capable of differentiation. Consistent with other cell types, late passages mTR(-/-)MSCs underwent senescence and were accompanied by telomere loss and chromosomal end-to-end fusions. These results suggest that in addition to its known role in cell replication, telomerase is required for differentiation of mMSCs in vitro. This work may be significant for further potentiating adult stem cells for use in tissue engineering and gene therapy and for understanding the significance of telomerase expression in the process of cell differentiation.
端粒酶活性的表达可能参与维持干细胞的自我复制和未分化状态。成年小鼠骨髓间充质干细胞（mMSCs）是多能细胞，能够分化为多种谱系细胞类型，包括脂肪细胞和软骨细胞。在此我们表明，mMSC缺乏端粒酶会丧失多能性和分化能力。mMSCs的原代培养物取自端粒酶敲除（mTR(-/-)）小鼠和野生型（WT）小鼠。从mTR(-/-)小鼠分离的间充质干细胞即使在早期传代时也无法分化为脂肪细胞和软骨细胞，而野生型间充质干细胞具有分化能力。与其他细胞类型一致，晚期传代的mTR(-/-)间充质干细胞会发生衰老，并伴有端粒丢失和染色体端端融合。这些结果表明，除了其在细胞复制中的已知作用外，端粒酶对于mMSCs在体外的分化也是必需的。这项工作对于进一步增强成体干细胞在组织工程和基因治疗中的应用以及理解端粒酶表达在细胞分化过程中的意义可能具有重要意义。
