Cargando…

Chromatin-mediated translational control is essential for neural cell fate specification

Neural cell fate specification is a multistep process in which stem cells undergo sequential changes in states, giving rise to particular lineages such as neurons and astrocytes. This process is accompanied by dynamic changes of chromatin and in transcription, thereby orchestrating lineage-specific...

Descripción completa

Detalles Bibliográficos
Autores principales: Hwang, Dong-Woo, Jaganathan, Anbalagan, Shrestha, Padmina, Jin, Ying, El-Amine, Nour, Wang, Sidney H, Hammell, Molly, Mills, Alea A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238594/
https://www.ncbi.nlm.nih.gov/pubmed/30456361
http://dx.doi.org/10.26508/lsa.201700016
_version_ 1783371414611427328
author Hwang, Dong-Woo
Jaganathan, Anbalagan
Shrestha, Padmina
Jin, Ying
El-Amine, Nour
Wang, Sidney H
Hammell, Molly
Mills, Alea A
author_facet Hwang, Dong-Woo
Jaganathan, Anbalagan
Shrestha, Padmina
Jin, Ying
El-Amine, Nour
Wang, Sidney H
Hammell, Molly
Mills, Alea A
author_sort Hwang, Dong-Woo
collection PubMed
description Neural cell fate specification is a multistep process in which stem cells undergo sequential changes in states, giving rise to particular lineages such as neurons and astrocytes. This process is accompanied by dynamic changes of chromatin and in transcription, thereby orchestrating lineage-specific gene expression programs. A pressing question is how these events are interconnected to sculpt cell fate. We show that altered chromatin due to loss of the chromatin remodeler Chd5 causes neural stem cell activation to occur ahead of time. This premature activation is accompanied by transcriptional derepression of ribosomal subunits, enhanced ribosome biogenesis, and increased translation. These untimely events deregulate cell fate decisions, culminating in the generation of excessive numbers of astrocytes at the expense of neurons. By monitoring the proneural factor Mash1, we further show that translational control is crucial for appropriate execution of cell fate specification, thereby providing new insight into the interplay between transcription and translation at the initial stages of neurogenesis.
format Online
Article
Text
id pubmed-6238594
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Life Science Alliance LLC
record_format MEDLINE/PubMed
spelling pubmed-62385942018-11-19 Chromatin-mediated translational control is essential for neural cell fate specification Hwang, Dong-Woo Jaganathan, Anbalagan Shrestha, Padmina Jin, Ying El-Amine, Nour Wang, Sidney H Hammell, Molly Mills, Alea A Life Sci Alliance Research Articles Neural cell fate specification is a multistep process in which stem cells undergo sequential changes in states, giving rise to particular lineages such as neurons and astrocytes. This process is accompanied by dynamic changes of chromatin and in transcription, thereby orchestrating lineage-specific gene expression programs. A pressing question is how these events are interconnected to sculpt cell fate. We show that altered chromatin due to loss of the chromatin remodeler Chd5 causes neural stem cell activation to occur ahead of time. This premature activation is accompanied by transcriptional derepression of ribosomal subunits, enhanced ribosome biogenesis, and increased translation. These untimely events deregulate cell fate decisions, culminating in the generation of excessive numbers of astrocytes at the expense of neurons. By monitoring the proneural factor Mash1, we further show that translational control is crucial for appropriate execution of cell fate specification, thereby providing new insight into the interplay between transcription and translation at the initial stages of neurogenesis. Life Science Alliance LLC 2018-08-23 /pmc/articles/PMC6238594/ /pubmed/30456361 http://dx.doi.org/10.26508/lsa.201700016 Text en © 2018 Hwang et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Hwang, Dong-Woo
Jaganathan, Anbalagan
Shrestha, Padmina
Jin, Ying
El-Amine, Nour
Wang, Sidney H
Hammell, Molly
Mills, Alea A
Chromatin-mediated translational control is essential for neural cell fate specification
title Chromatin-mediated translational control is essential for neural cell fate specification
title_full Chromatin-mediated translational control is essential for neural cell fate specification
title_fullStr Chromatin-mediated translational control is essential for neural cell fate specification
title_full_unstemmed Chromatin-mediated translational control is essential for neural cell fate specification
title_short Chromatin-mediated translational control is essential for neural cell fate specification
title_sort chromatin-mediated translational control is essential for neural cell fate specification
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238594/
https://www.ncbi.nlm.nih.gov/pubmed/30456361
http://dx.doi.org/10.26508/lsa.201700016
work_keys_str_mv AT hwangdongwoo chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT jaganathananbalagan chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT shresthapadmina chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT jinying chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT elaminenour chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT wangsidneyh chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT hammellmolly chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification
AT millsaleaa chromatinmediatedtranslationalcontrolisessentialforneuralcellfatespecification