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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...

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Autores principales: Ishaq, Abbas, Hanson, Peter S., Morris, Christopher M., Saretzki, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929426/
https://www.ncbi.nlm.nih.gov/pubmed/27322326
http://dx.doi.org/10.3390/genes7060027
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author Ishaq, Abbas
Hanson, Peter S.
Morris, Christopher M.
Saretzki, Gabriele
author_facet Ishaq, Abbas
Hanson, Peter S.
Morris, Christopher M.
Saretzki, Gabriele
author_sort Ishaq, Abbas
collection PubMed
description 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.
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spelling pubmed-49294262016-07-07 Telomerase Activity is Downregulated Early During Human Brain Development Ishaq, Abbas Hanson, Peter S. Morris, Christopher M. Saretzki, Gabriele Genes (Basel) Article 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. MDPI 2016-06-16 /pmc/articles/PMC4929426/ /pubmed/27322326 http://dx.doi.org/10.3390/genes7060027 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ishaq, Abbas
Hanson, Peter S.
Morris, Christopher M.
Saretzki, Gabriele
Telomerase Activity is Downregulated Early During Human Brain Development
title Telomerase Activity is Downregulated Early During Human Brain Development
title_full Telomerase Activity is Downregulated Early During Human Brain Development
title_fullStr Telomerase Activity is Downregulated Early During Human Brain Development
title_full_unstemmed Telomerase Activity is Downregulated Early During Human Brain Development
title_short Telomerase Activity is Downregulated Early During Human Brain Development
title_sort telomerase activity is downregulated early during human brain development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929426/
https://www.ncbi.nlm.nih.gov/pubmed/27322326
http://dx.doi.org/10.3390/genes7060027
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