Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression

© 2018. Published by The Company of Biologists Ltd. Our understanding of the transcriptional programme underpinning adult hippocampal neurogenesis is incomplete. In mice, under basal conditions, adult hippocampal neural stem cells (AH-NSCs) generate neurons and astrocytes, but not oligodendrocytes....

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Main Authors: Harris, L., Zalucki, O., Clément, O., Fraser, J., Matuzelski, E., Oishi, S., Harvey, T., Burne, T., Heng, Julian, Gronostajski, R., Piper, M.
Format: Journal Article
Published: Company of Biologists LTD 2018
Online Access:http://hdl.handle.net/20.500.11937/71683
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author Harris, L.
Zalucki, O.
Clément, O.
Fraser, J.
Matuzelski, E.
Oishi, S.
Harvey, T.
Burne, T.
Heng, Julian
Gronostajski, R.
Piper, M.
author_facet Harris, L.
Zalucki, O.
Clément, O.
Fraser, J.
Matuzelski, E.
Oishi, S.
Harvey, T.
Burne, T.
Heng, Julian
Gronostajski, R.
Piper, M.
author_sort Harris, L.
building Curtin Institutional Repository
collection Online Access
description © 2018. Published by The Company of Biologists Ltd. Our understanding of the transcriptional programme underpinning adult hippocampal neurogenesis is incomplete. In mice, under basal conditions, adult hippocampal neural stem cells (AH-NSCs) generate neurons and astrocytes, but not oligodendrocytes. The factors limiting oligodendrocyte production, however, remain unclear. Here, we reveal that the transcription factor NFIX plays a key role in this process. NFIX is expressed by AH-NSCs, and its expression is sharply upregulated in adult hippocampal neuroblasts. Conditional ablation of Nfix from AH-NSCs, coupled with lineage tracing, transcriptomic sequencing and behavioural studies collectively reveal that NFIX is cell-autonomously required for neuroblast maturation and survival. Moreover, a small number of AH-NSCs also develop into oligodendrocytes following Nfix deletion. Remarkably, when Nfix is deleted specifically from intermediate progenitor cells and neuroblasts using a Dcx-creERT2driver, these cells also display elevated signatures of oligodendrocyte gene expression. Together, these results demonstrate the central role played by NFIX in neuroblasts within the adult hippocampal stem cell neurogenic niche in promoting the maturation and survival of these cells, while concomitantly repressing oligodendrocyte gene expression signatures.
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spelling curtin-20.500.11937-716832018-12-13T09:33:29Z Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression Harris, L. Zalucki, O. Clément, O. Fraser, J. Matuzelski, E. Oishi, S. Harvey, T. Burne, T. Heng, Julian Gronostajski, R. Piper, M. © 2018. Published by The Company of Biologists Ltd. Our understanding of the transcriptional programme underpinning adult hippocampal neurogenesis is incomplete. In mice, under basal conditions, adult hippocampal neural stem cells (AH-NSCs) generate neurons and astrocytes, but not oligodendrocytes. The factors limiting oligodendrocyte production, however, remain unclear. Here, we reveal that the transcription factor NFIX plays a key role in this process. NFIX is expressed by AH-NSCs, and its expression is sharply upregulated in adult hippocampal neuroblasts. Conditional ablation of Nfix from AH-NSCs, coupled with lineage tracing, transcriptomic sequencing and behavioural studies collectively reveal that NFIX is cell-autonomously required for neuroblast maturation and survival. Moreover, a small number of AH-NSCs also develop into oligodendrocytes following Nfix deletion. Remarkably, when Nfix is deleted specifically from intermediate progenitor cells and neuroblasts using a Dcx-creERT2driver, these cells also display elevated signatures of oligodendrocyte gene expression. Together, these results demonstrate the central role played by NFIX in neuroblasts within the adult hippocampal stem cell neurogenic niche in promoting the maturation and survival of these cells, while concomitantly repressing oligodendrocyte gene expression signatures. 2018 Journal Article http://hdl.handle.net/20.500.11937/71683 10.1242/dev.155689 Company of Biologists LTD restricted
spellingShingle Harris, L.
Zalucki, O.
Clément, O.
Fraser, J.
Matuzelski, E.
Oishi, S.
Harvey, T.
Burne, T.
Heng, Julian
Gronostajski, R.
Piper, M.
Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title_full Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title_fullStr Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title_full_unstemmed Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title_short Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
title_sort neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by nfix expression
url http://hdl.handle.net/20.500.11937/71683