Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells.
Human bone marrow mesenchymal stem cells (hMSCs) are a promising source for clinical stem cell transplantation. However, telomere regulation mechanisms, as one of the possible major mechanisms by which hMSCs sustain their stem cell characteristics, remain unknown. We isolated hMSCs by plastic adhesion and characterized these cells by morphology, immune phenotype and differentiation capacity. Telomerase was found negative in hMSCs, but slightly up-regulated in hMSC-derived adipocytes by the Telomeric Repeat Amplification Protocol (TRAP) assay. Moreover, hMSCs lack the alternative lengthening of telomeres (ALT) mechanism, because the hallmarks of ALT, such as very long and heterogeneous telomeres, extra-chromosome telomere repeat DNA (ECTR), and ALT-associated promyelocytic leukemia bodies (APBs), were not evident. However, when hMSCs were arrested in S phase with a combination of serum deprivation and aphidicolin, previously undetectable telomerase activity became predominantly positive. Meanwhile, the expression level of hTERT protein and mRNA increased, paralleled with the appearance of a large cohort of synchronized hMSCs at S phase. These findings provide a profile of telomere regulation by cell cycle dependent expression of telomerase in hMSCs and may lead to a better understanding of the stem cell nature of these cells.
Zhao
Yan-Min
YM
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
Li
Jing-Yuan
JY
Lan
Jian-Ping
JP
Lai
Xiao-Yu
XY
Luo
Yi
Y
Sun
Jie
J
Yu
Jian
J
Zhu
Yuan-Yuan
YY
Zeng
Fen-Fang
FF
Zhou
Qian
Q
Huang
He
H
D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D010641:Phenotype; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
C509186:TERT protein, human; D019098:Telomerase