He Caixia, Zhang Xiaorui, Li Jin, Dai Conglin, Wang Siqi, Dai Can, Zeng Sicong
Hunan Guangxiu Hospital, School of Medicine, Hunan Normal University, Changsha, 410001, Hunan, China; National Engineering and Research Center of Human Stem Cells, Changsha, 410001, Hunan, China.
Hunan Guangxiu Hospital, School of Medicine, Hunan Normal University, Changsha, 410001, Hunan, China.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 2):40-47. doi: 10.1016/j.bbrc.2022.10.093. Epub 2022 Oct 31.
Telomerase is activated in pluripotent stem cells and the majority of tumors and is postulated to be necessary for the acquisition of self-renewal and long-term proliferation. Placental mesenchymal stem cells (PMSCs) are very promising in regenerative medicine owing to their great capacity for self-renewal and differentiation potential. Although telomerase activity in the placenta is naturally low, it remains unclear whether telomerase activity is required for the properties of PMSCs. We herein isolated and identified a PMSC line carrying compound heterozygote variations in hTERT (DC-PMSCs) that lost telomerase activity, showed a typical surface phenotype of MSCs, and was able to differentiate into multiple cell lineages. DC-PMSCs showed accelerated telomere erosion, advanced senescence, and diminished migratory and invasive capabilities. RNA-seq identified 361 differentially expressed genes between DC-PMSCs and control groups, most of which were enriched in extracellular matrix, ECM, and related pathways. Knockdown of telomerase subunit genes in PMSCs confirmed the phenotype and attenuated the expression of extracellular matrix components and matrix metalloproteases. Our results suggest that low telomerase activity is not essential for the properties of MSCs, but that it is required for community maintenance and for the migration of PMSCs.
端粒酶在多能干细胞和大多数肿瘤中被激活，据推测它对于获得自我更新和长期增殖是必需的。胎盘间充质干细胞（PMSC）因其强大的自我更新能力和分化潜能，在再生医学中极具前景。尽管胎盘中的端粒酶活性天然较低，但PMSC的特性是否需要端粒酶活性仍不清楚。我们在此分离并鉴定了一株在hTERT中携带复合杂合变异的PMSC系（DC-PMSC），该细胞系失去了端粒酶活性，表现出典型的间充质干细胞表面表型，并且能够分化为多种细胞谱系。DC-PMSC表现出加速的端粒侵蚀、提前衰老以及迁移和侵袭能力减弱。RNA测序确定了DC-PMSC与对照组之间361个差异表达基因，其中大多数在细胞外基质、ECM及相关途径中富集。敲低PMSC中端粒酶亚基基因证实了该表型，并减弱了细胞外基质成分和基质金属蛋白酶的表达。我们的结果表明，低水平的端粒酶活性对于间充质干细胞的特性并非必不可少，但对于PMSC的群体维持和迁移是必需的。
