Telomerase Activity is Downregulated Early During Human Brain Development.
Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6-19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw.
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. A.Ishaq1@newcastle.ac.uk.|Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. A.Ishaq1@newcastle.ac.uk.
Abbas
A
Ishaq
Health Protection Research Unit, Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. peter.hanson@newcastle.ac.uk.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. peter.hanson@newcastle.ac.uk.
Peter S
PS
Hanson
Health Protection Research Unit, Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. c.m.morris@newcastle.ac.uk.|Institute of Neurosciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. c.m.morris@newcastle.ac.uk.
Christopher M
CM
Morris
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. gabriele.saretzki@ncl.ac.uk.|Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE1 7RU, UK. gabriele.saretzki@ncl.ac.uk.
Gabriele
G
Saretzki
brain; development; expression; hTERT splice-variants; hTR; neural stem cells; telomerase activity